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RNA splicing
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The maturation process of the primary RNA transcript to remove intron sequences (not present in the mature form) and joining the remaining exon sections to form the mature messenger RNA
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RNA splicing, in molecular biology, is a form of RNA processing in which a newly made precursor messenger RNA (pre-mRNA) transcript is transformed into a mature messenger RNA (mRNA). During splicing, introns are removed and exons are joined together. For nuclear-encoded genes, splicing takes place within the nucleus either during or immediately after transcription. For those eukaryotic genes that contain introns, splicing is usually required in order to create an mRNA molecule that can be translated into protein. For many eukaryotic introns, splicing is carried out in a series of reactions which are catalyzed by the spliceosome, a complex of small nuclear ribonucleo proteins (snRNPs). Self-splicing introns, or ribozymes capable of catalyzing their own excision from their parent RNA molecule, also exist.
Contents
1 Splicing pathways
1.1 Spliceosomal
1.1.1 Introns
1.1.2 Formation and activity
1.2 Recursive splicing
1.3 Self-splicing
1.4 tRNA splicing
2 Evolution
3 Biochemical mechanism
4 Alternative splicing
5 Splicing response to DNA damage
6 Experimental manipulation of splicing
7 Splicing errors and variation
8 Protein splicing
9 See also
10 References
11 External links
Splicing pathways[edit]
Several methods of RNA splicing occur in nature; the type of splicing depends on the structure of the spliced intron and the catalysts required for splicing to occur.
Spliceosomal[edit]
Introns[edit]
The word intron is derived from the term intervening sequence, that is, a segment of DNA that "intervenes" between two exons of a gene. The term intron refers to both the DNA sequence within a gene and the corresponding sequence in the unprocessed RNA transcript. As part of the RNA processing pathway, introns are removed by RNA splicing either shortly after or concurrent with transcription.[1] Introns are found in the genes of most organisms and many viruses. They can be located in a wide range of genes, including those that generate proteins, ribosomal RNA (rRNA), and transfer RNA (tRNA).[2]
Spliceosomal introns often reside within the sequence of eukaryotic protein-coding genes. Within the intron, a donor site (5' end of the intron), a branch site (near the 3' end of the intron) and an acceptor site (3' end of the intron) are required for splicing. The splice donor site includes an almost invariant sequence GU at the 5' end of the intron, within a larger, less highly conserved region. The splice acceptor site at the 3' end of the intron terminates the intron with an almost invariant AG sequence. Upstream (5'-ward) from the AG there is a region high in pyrimidines (C and U), or polypyrimidine tract. Further upstream from the polypyrimidine tract is the branchpoint, which includes an adenine nucleotide involved in lariat formation.[3][4] The consensus sequence for an intron (in IUPAC nucleic acid notation) is: G-G-[cut]-G-U-R-A-G-U (donor site) ... intron sequence ... Y-U-R-A-C (branch sequence 20-50 nucleotides upstream of acceptor site) ... Y-rich-N-C-A-G-[cut]-G (acceptor site).[5] However, it is noted that the specific sequence of intronic splicing elements and the number of nucleotides between the branchpoint and the nearest 3’ acceptor site affect splice site selection.[6][7] Also, point mutations in the underlying DNA or errors during transcription can activate a cryptic splice site in part of the transcript that usually is not spliced. This results in a mature messenger RNA with a missing section of an exon. In this way, a point mutation, which might otherwise affect only a single amino acid, can manifest as a deletion or truncation in the final protein.
Simple illustration of exons and introns in pre-mRNA
Formation and activity[edit]
Splicing is catalyzed by the spliceosome, a large RNA-protein complex composed of five small nuclear ribonucleoproteins (snRNPs, pronounced 'snurps'). Assembly and activity of the spliceosome occurs during transcription of the pre-mRNA. The RNA components of snRNPs interact with the intron and are involved in catalysis. Two types of spliceosomes have been identified (major and minor) which contain different snRNPs.
The major spliceosome splices introns containing GU at the 5' splice site and AG at the 3' splice site. It is composed of the U1, U2, U4, U5, and U6 snRNPs and is active in the nucleus. In addition, a number of proteins including U2 small nuclear RNA auxiliary factor 1 (U2AF35), U2AF2 (U2AF65)[8] and SF1 are required for the assembly of the spliceosome.[4][9] The spliceosome forms different complexes during the splicing process:[10]
Complex E
The U1 snRNP binds to the GU sequence at the 5' splice site of an intron;
Splicing factor 1 binds to the intron branch point sequence;
U2AF1 binds at the 3' splice site of the intron;
U2AF2 binds to the polypyrimidine tract;[11]
Complex A (pre-spliceosome)
The U2 snRNP displaces SF1 and binds to the branch point sequence and ATP is hydrolyzed;
Complex B (pre-catalytic spliceosome)
The U5/U4/U6 snRNP trimer binds, and the U5 snRNP binds exons at the 5' site, with U6 binding to U2;
Complex B*
The U1 snRNP is released, U5 shifts from exon to intron, and the U6 binds at the 5' splice site;
Complex C (catalytic spliceosome)
U4 is released, U6/U2 catalyzes transesterification, making the 5'-end of the intron ligate to the A on intron and form a lariat, U5 binds exon at 3' splice site, and the 5' site is cleaved, resulting in the formation of the lariat;
Complex C* (post-spliceosomal complex)
U2/U5/U6 remain bound to the lariat, and the 3' site is cleaved and exons are ligated using ATP hydrolysis. The spliced RNA is released, the lariat is released and degraded,[12] and the snRNPs are recycled.
This type of splicing is termed canonical splicing or termed the lariat pathway, which accounts for more than 99% of splicing. By contrast, when the intronic flanking sequences do not follow the GU-AG rule, noncanonical splicing is said to occur (see "minor spliceosome" below).[13]
The minor spliceosome is very similar to the major spliceosome, but instead it splices out rare introns with different splice site sequences. While the minor and major spliceosomes contain the same U5 snRNP, the minor spliceosome has different but functionally analogous snRNPs for U1, U2, U4, and U6, which are respectively called U11, U12, U4atac, and U6atac.[14]
Trans-splicing is a form of splicing that joins two exons that are not within the same RNA transcript.[15]
Recursive splicing[edit]
In most cases, splicing removes introns as single units from precursor mRNA transcripts. However, in some cases, especially in mRNAs with very long introns, splicing happens in steps, with part of an intron removed and then the remaining intron is spliced out in a following step. This has been found first in the Ultrabithorax (Ubx) gene of the fruit fly, Drosophila melanogaster, and a few other Drosophila genes, but cases in human have been reported as well.[16][17]
Self-splicing[edit]
Self-splicing occurs for rare introns that form a ribozyme, performing the functions of the spliceosome by RNA alone. There are three kinds of self-splicing introns, Group I, Group II and Group III. Group I and II introns perform splicing similar to the spliceosome without requiring any protein. This similarity suggests that Group I and II introns may be evolutionarily related to the spliceosome. Self-splicing may also be very ancient, and may have existed in an RNA world present before protein.
Two transesterifications characterize the mechanism in which group I introns are spliced:
3'OH of a free guanine nucleoside (or one located in the intron) or a nucleotide cofactor (GMP, GDP, GTP) attacks phosphate at the 5' splice site.
3'OH of the 5' exon becomes a nucleophile and the second transesterification results in the joining of the two exons.
The mechanism in which group II introns are spliced (two transesterification reaction like group I introns) is as follows:
The 2'OH of a specific adenosine in the intron attacks the 5' splice site, thereby forming the lariat
The 3'OH of the 5' exon triggers the second transesterification at the 3' splice site, thereby joining the exons together.
tRNA splicing[edit]
tRNA (also tRNA-like) splicing is another rare form of splicing that usually occurs in tRNA. The splicing reaction involves a different biochemistry than the spliceosomal and self-splicing pathways.
In the yeast Saccharomyces cerevisiae, a yeast tRNA splicing endonuclease heterotetramer, composed of TSEN54, TSEN2, TSEN34, and TSEN15, cleaves pre-tRNA at two sites in the acceptor loop to form a 5'-half tRNA, terminating at a 2',3'-cyclic phosphodiester group, and a 3'-half tRNA, terminating at a 5'-hydroxyl group, along with a discarded intron.[18] Yeast tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA cyclic phosphodiesterase cleaves the cyclic phosphodiester group to form a 2'-phosphorylated 3' end. Yeast tRNA ligase adds an adenosine monophosphate group to the 5' end of the 3'-half and joins the two halves together.[19] NAD-dependent 2'-phosphotransferase then removes the 2'-phosphate group.[20][21]
Evolution[edit]
Splicing occurs in all the kingdoms or domains of life, however, the extent and types of splicing can be very different between the major divisions. Eukaryotes splice many protein-coding messenger RNAs and some non-coding RNAs. Prokaryotes, on the other hand, splice rarely and mostly non-coding RNAs. Another important difference between these two groups of organisms is that prokaryotes completely lack the spliceosomal pathway.
Because spliceosomal introns are not conserved in all species, there is debate concerning when spliceosomal splicing evolved. Two models have been proposed: the intron late and intron early models (see intron evolution).
Splicing diversity
Eukaryotes
Prokaryotes
Spliceosomal + −
Self-splicing + +
tRNA + +
Biochemical mechanism[edit]
Diagram illustrating the two-step biochemistry of splicing
Spliceosomal splicing and self-splicing involve a two-step biochemical process. Both steps involve transesterification reactions that occur between RNA nucleotides. tRNA splicing, however, is an exception and does not occur by transesterification.[22]
Spliceosomal and self-splicing transesterification reactions occur via two sequential transesterification reactions. First, the 2'OH of a specific branchpoint nucleotide within the intron, defined during spliceosome assembly, performs a nucleophilic attack on the first nucleotide of the intron at the 5' splice site, forming the lariat intermediate. Second, the 3'OH of the released 5' exon then performs a nucleophilic attack at the first nucleotide following the last nucleotide of the intron at the 3' splice site, thus joining the exons and releasing the intron lariat.[23]
Alternative splicing[edit]
Main article: Alternative splicing
In many cases, the splicing process can create a range of unique proteins by varying the exon composition of the same mRNA. This phenomenon is then called alternative splicing. Alternative splicing can occur in many ways. Exons can be extended or skipped, or introns can be retained. It is estimated that 95% of transcripts from multiexon genes undergo alternative splicing, some instances of which occur in a tissue-specific manner and/or under specific cellular conditions.[24] Development of high throughput mRNA sequencing technology can help quantify the expression levels of alternatively spliced isoforms. Differential expression levels across tissues and cell lineages allowed computational approaches to be developed to predict the functions of these isoforms.[25][26] Given this complexity, alternative splicing of pre-mRNA transcripts is regulated by a system of trans-acting proteins (activators and repressors) that bind to cis-acting sites or "elements" (enhancers and silencers) on the pre-mRNA transcript itself. These proteins and their respective binding elements promote or reduce the usage of a particular splice site. The binding specificity comes from the sequence and structure of the cis-elements, e.g. in HIV-1 there are many donor and acceptor splice sites. Among the various splice sites, ssA7, which is 3' acceptor site, folds into three stem loop structures, i.e. Intronic splicing silencer (ISS), Exonic splicing enhancer (ESE), and Exonic splicing silencer (ESSE3). Solution structure of Intronic splicing silencer and its interaction to host protein hnRNPA1 give insight into specific recognition.[27] However, adding to the complexity of alternative splicing, it is noted that the effects of regulatory factors are many times position-dependent. For example, a splicing factor that serves as a splicing activator when bound to an intronic enhancer element may serve as a repressor when bound to its splicing element in the context of an exon, and vice versa.[28] In addition to the position-dependent effects of enhancer and silencer elements, the location of the branchpoint (i.e., distance upstream of the nearest 3’ acceptor site) also affects splicing.[6] The secondary structure of the pre-mRNA transcript also plays a role in regulating splicing, such as by bringing together splicing elements or by masking a sequence that would otherwise serve as a binding element for a splicing factor.[29][30]
Splicing response to DNA damage[edit]
DNA damage affects splicing factors by altering their post-translational modification, localization, expression and activity.[31] Furthermore, DNA damage often disrupts splicing by interfering with its coupling to transcription. DNA damage also has an impact on the splicing and alternative splicing of genes intimately associated with DNA repair.[31] For instance, DNA damages modulate the alternative splicing of the DNA repair genes Brca1 and Ercc1.
Experimental manipulation of splicing[edit]
Splicing events can be experimentally altered[32][33] by binding steric-blocking antisense oligos such as Morpholinos or Peptide nucleic acids to snRNP binding sites, to the branchpoint nucleotide that closes the lariat,[34] or to splice-regulatory element binding sites.[35]
Splicing errors and variation[edit]
It has been suggested that one third of all disease-causing mutations impact on splicing.[28] Common errors include:
Mutation of a splice site resulting in loss of function of that site. Results in exposure of a premature stop codon, loss of an exon, or inclusion of an intron.
Mutation of a splice site reducing specificity. May result in variation in the splice location, causing insertion or deletion of amino acids, or most likely, a disruption of the reading frame.
Displacement of a splice site, leading to inclusion or exclusion of more RNA than expected, resulting in longer or shorter exons.
Although many splicing errors are safeguarded by a cellular quality control mechanism termed nonsense-mediated mRNA decay (NMD),[36] a number of splicing-related diseases also exist, as suggested above.[37]
Allelic differences in mRNA splicing are likely to be a common and important source of phenotypic diversity at the molecular level, in addition to their contribution to genetic disease susceptibility. Indeed, genome-wide studies in humans have identified a range of genes that are subject to allele-specific splicing.
Protein splicing[edit]
Main article: Protein splicing
In addition to RNA, proteins can undergo splicing. Although the biomolecular mechanisms are different, the principle is the same: parts of the protein, called inteins instead of introns, are removed. The remaining parts, called exteins instead of exons, are fused together. Protein splicing has been observed in a wide range of organisms, including bacteria, archaea, plants, yeast and humans.[38]
See also[edit]
Wikimedia Commons has media related to Splicing.
cDNA
Exon junction complex
mRNA capping
Polyadenylation
Post-transcriptional modification
RNA editing
SWAP protein domain, a splicing regulator
References[edit]
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External links[edit]
Virtual Cell Animation Collection: mRNA Splicing
RNA+Splicing at the US National Library of Medicine Medical Subject Headings (MeSH)
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text:
Dust on the Bottle
From Wikipedia, the free encyclopedia
Jump to: navigation, search
"Dust on the Bottle"
Single by David Lee Murphy
from the album Out with a Bang
B-side
"Mama 'n Them"[1]
Released
August 7, 1995
Format
Cassette single
Recorded
1994
Genre
Country, country rock
Length
3:44
Label
MCA
Songwriter(s)
David Lee Murphy
Producer(s)
Tony Brown
David Lee Murphy singles chronology
"Party Crowd"
(1995) "Dust on the Bottle"
(1995) "Out with a Bang"
(1995)
"Party Crowd"
(1995) "Dust on the Bottle"
(1995) "Out with a Bang"
(1995)
"Dust on the Bottle" is a song written and recorded by American country music artist David Lee Murphy. It was released in August 1995 as the fourth single from the album Out with a Bang. The song hit number one on the Billboard Hot Country Singles & Tracks in late 1995[2] and is Murphy's only number one hit. The song also hit number 9 on the Canadian Country charts.
Contents
[hide]
1 Background and writing
2 Content
3 Music video
4 Chart positions
4.1 Year-end charts
5 References
Background and writing[edit]
In an interview with The Boot, Murphy said that he was playing guitar at his kitchen table in the morning and the song "came out of nowhere." Murphy goes on to say that he wrote the song in 15 minutes.[3]
Content[edit]
The song is about an old man named Creole Williams. The narrator asks him for advice on impressing his lover, and Williams gives him a bottle of homemade wine, then tells him "There might be a little dust on the bottle / But it's one of those things that gets sweeter with time".
Music video[edit]
The music video was directed by Charley Randazzo and premiered in mid-1995.
Chart positions[edit]
"Dust on the Bottle" debuted at number 72 on the U.S. Billboard Hot Country Singles & Tracks for the week of August 12, 1995.
Chart (1995)
Peak
position
Canada Country Tracks (RPM)[4] 9
US Hot Country Songs (Billboard)[5] 1
Year-end charts[edit]
Chart (1995)
Position
US Country Songs (Billboard)[6] 37
Preceded by
"She's Every Woman"
by Garth Brooks Billboard Hot Country Singles & Tracks
number-one single
October 28-November 4, 1995 Succeeded by
"Check Yes or No"
by George Strait
References[edit]
Jump up ^ Whitburn, Joel (2008). Hot Country Songs 1944 to 2008. Record Research, Inc. p. 290. ISBN 0-89820-177-2.
Jump up ^ Billboard
Jump up ^ Conaway, Alanna (13 November 2010). "David Lee Murphy, 'Dust on the Bottle' — Story Behind the Lyrics". The Boot. Retrieved 3 December 2010.
Jump up ^ "Top RPM Country Tracks: Issue 2805." RPM. Library and Archives Canada. November 13, 1995. Retrieved July 21, 2013.
Jump up ^ "David Lee Murphy – Chart history" Billboard Hot Country Songs for David Lee Murphy.
Jump up ^ "Best of 1995: Country Songs". Billboard. Prometheus Global Media. 1995. Retrieved July 21, 2013.
[hide]
v
t
e
David Lee Murphy
Studio albums
Out with a Bang
Gettin' Out the Good Stuff
We Can't All Be Angels
Tryin' to Get There
Notable singles
"Party Crowd"
"Dust on the Bottle"
"Out with a Bang"
"Every Time I Get Around You"
"The Road You Leave Behind"
"All Lit Up in Love"
"Just Don't Wait Around 'Til She's Leavin'"
"Loco"
Related articles
List of songs written by David Lee Murphy
This 1990s country song-related article is a stub. You can help Wikipedia by expanding it.
v
t
e
Retrieved from "https://en.wikipedia.org/w/index.php?title=Dust_on_the_Bottle&oldid=776288185"
Categories:
1995 singles
Billboard Hot Country Songs number-one singles
1995 songs
David Lee Murphy songs
Songs written by David Lee Murphy
Song recordings produced by Tony Brown (record producer)
MCA Records singles
Country rock songs
Songs about alcohol
1990s country song stubs
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text:
Investigational New Drug
From Wikipedia, the free encyclopedia
Jump to navigation Jump to search
Regulation of therapeutic goods in the United States
Prescription drugs
Over-the-counter drugs
Law[show]
Federal Food, Drug, and Cosmetic Act
Comprehensive Drug Abuse Prevention and Control Act of 1970
Controlled Substances Act
Prescription Drug Marketing Act
Drug Price Competition and Patent Term Restoration Act
Hatch-Waxman exemption
Marihuana Tax Act
Government agencies[show]
Department of Health and Human Services
Food and Drug Administration
Department of Justice
Drug Enforcement Administration
Process[show]
Drug discovery
Drug design
Drug development
New drug application
Investigational new drug
Clinical trial (Phase I, II, III, IV)
Randomized controlled trial
Pharmacovigilance
Abbreviated New Drug Application
Fast track approval
Off-label use
International coordination[show]
International Conference on Harmonisation of Technical
Requirements for Registration of Pharmaceuticals for Human Use
Uppsala Monitoring Centre
World Health Organization
Council for International Organizations of Medical Sciences
Single Convention on Narcotic Drugs
Non-governmental organizations[show]
Institute of Medicine
Research on Adverse Drug events And Reports
NORML
v
t
e
The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug across state lines (usually to clinical investigators) before a marketing application for the drug has been approved. Regulations are primarily at 21 C.F.R. 312. Similar procedures are followed in the European Union, Japan, and Canada.
Contents
1 Types
2 Application
3 Miscellaneous
4 Examples
5 See also
6 References
7 External links
Types[edit]
Timeline for drug evaluation
Commercial INDs are filed by companies to obtain marketing approval for a new drug.
Research or Investigator INDs are non-commercial INDs filed by researchers to study an unapproved drug or to study an approved drug for a new indication or in a new patient population.
Emergency Use INDs, also called compassionate use or single-patient INDs, are filed for emergency use of an unapproved drug when the clinical situation does not allow sufficient time to submit an IND in accordance with 21 CFR §§ 312.23, 312.24. These are most commonly used for life-threatening conditions for which there is no standard treatment.
Treatment INDs are filed to make a drug available for treatment of serious or immediately life-threatening conditions prior to FDA approval. Serious diseases or conditions are stroke, schizophrenia, rheumatoid arthritis, osteoarthritis, chronic depression, seizures, Alzheimer's dementia, amyotrophic lateral sclerosis (ALS), and narcolepsy.
Screening INDs are filed for multiple, closely related compounds in order to screen for the preferred compounds or formulations. The preferred compound can then be developed under a separate IND. Used for screening different salts, esters and other drug derivatives that are chemically different, but pharmacodynamically similar.
Application[edit]
The IND application may be divided into the following categories:[1]
Preclinical Testing consists of animal pharmacology and toxicology studies to assess whether the drug is safe for testing in humans. Also included are any previous experience with the drug in humans (often foreign use).
Manufacturing Information includes composition, manufacturer, and stability of, and the controls used for, manufacturing the drug. Used to ensure that the company can adequately produce and supply consistent batches of the drug.
Investigator Information on the qualifications of clinical investigators, that is, the professionals (generally physicians) who oversee the administration of the experimental drug to the study subjects. Used to assess whether the investigators are qualified to fulfill their clinical trial duties.
Clinical Trial Protocols are the centerpiece of the IND. Detailed protocols for proposed clinical studies to assess whether the initial-phase trials will expose the subjects to unnecessary risks.
Other Commitments are commitments to obtain informed consent from the research subjects, to obtain review of the study by an institutional review board (IRB), and to adhere to the investigational new drug regulations.
An IND must also include an Investigator's Brochure intended to educate the trial investigators of the significant facts about the trial drug they need to know to conduct their clinical trial with the least hazard to the subjects or patients.
Once an IND is submitted, the FDA has 30 days to object to the IND or it automatically becomes effective and clinical trials may begin. If the FDA detects a problem, it may place a clinical hold on the IND, prohibiting the start of the clinical studies until the problem is resolved.
Experimental drugs under an IND must be labeled "Caution: New Drug – Limited by Federal (or United States) law to investigational use."
Miscellaneous[edit]
Approximately two thirds of both investigational new drugs (INDs) and new drug applications (NDAs) are small-molecule drugs, the rest are biopharmaceuticals. About half of the investigational new drugs (INDs) fail in preclinical and clinical phases of drug development.
Examples[edit]
The FDA runs a medical marijuana IND program (the Compassionate Investigational New Drug program). It stopped accepting new patients in 1992 after public health authorities concluded there was no scientific value to it, and due to President George H.W. Bush administration's desire to "get tough on crime and drugs." As of 2011, four patients continue to receive cannabis from the government under the program.[2]
Sanctioned by Executive Order 13139, the US Department of Defense employed an anthrax vaccine classified as an investigational new drug (IND) in its Anthrax Vaccine Immunization Program (AVIP).
See also[edit]
Abigail Alliance for Better Access to Developmental Drugs
Drug Discovery
FDA Fast Track Development Program
Good Manufacturing Practice
Inverse benefit law
New drug application, after clinical trials
Biologics license application
Orphan drug
References[edit]
Jump up ^ John S. McInnes (2011), "New Drug Applications", in Shayne C. Gad, Pharmaceutical Sciences Encyclopedia, doi:10.1002/9780470571224.pse420
Jump up ^ "4 Americans get medical pot from the feds". CBS News. September 28, 2011.
External links[edit]
Investigational New Drug (IND) Application Process Center for Drug Evaluation and Research, Food and Drug Administration.
ICH Guidance for Industry, E6 Good Clinical Practice: Consolidated Guidance. BROKEN LINK
Troetel, W.M.: Achieving a Successful US IND Filing (1) The Regulatory Affairs Journal. 6: 22–28, January 1995.
Troetel, W.M.: Achieving a Successful US IND Filing (2) The Regulatory Affairs Journal. 6: 104–108, February 1995.
Henninger, Daniel (2002). "Drug Lag". In David R. Henderson (ed.). Concise Encyclopedia of Economics (1st ed.). Library of Economics and Liberty. CS1 maint: Extra text: editors list (link) OCLC 317650570, 50016270, 163149563
IND Forms and Instructions from the US Food and Drug Administration
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Indian Foreign Service
From Wikipedia, the free encyclopedia
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Indian Foreign Service
Service Overview
Formed
October 9, 1946
Headquarters
South Block, New Delhi
Country
India
Training Ground
Foreign Service Institute, New Delhi
Field of Operation
Controlling Authority
Ministry of External Affairs
Legal personality
Governmental: Government Services
General Nature
Diplomacy & Foreign policy
Economic diplomacy
Trade Relations
Defence Diplomacy
Cultural diplomacy
Consular Services
Public diplomacy
Intergovernmental organization
Preceding Service
Indian Civil Service
Cadre Size
770 IFS officers but in total 2,700 personnel holding diplomatic rank (2016)[1]
Service Chief
Foreign Secretary
Vijay Keshav Gokhale, IFS
Head of the Civil Services
Cabinet Secretary
Pradeep Kumar Sinha, IAS
The Indian Foreign Service is the administrative diplomatic[1] civil service under Group A[2] of the Central Civil Services of the executive branch of the Government of India. It is considered to be one of the two premier Civil Services (the other being the IAS), as appointment to IFS renders a person ineligible to reappear in Civil Services Examination.[3] It is a Central Civil service as Foreign policy is the subject matter and prerogative of Union Government.[4] The Ambassador, High Commissioner, Consul General, Permanent Representative of India to the United Nations and Foreign Secretary are some of the offices held by the members of this service.[1]
The service is entrusted to conduct diplomacy and manage foreign relations of India.[1] It is the body of career diplomats serving in more than 180 Indian Diplomatic Missions and International Organisations around the world. In addition, they serve at the headquarters of the Ministry of External affairs in Delhi and the Prime Minister's Office.[5] They also head the Regional Passport Offices throughout the country and hold positions in the President's Secretariat and several ministries on deputation. Foreign Secretary of India is the administrative head of the Indian Foreign Service.
IFS was created by the Government of India in October 1946 through a Cabinet note[6] but its roots can be traced back to the British Raj when the Foreign Department was created to conduct business with the "Foreign European Powers".[7] IFS Day is celebrated on October 9 every year since 2011 to commemorate the day the Indian Cabinet created the IFS.[6]
Officers of the IFS are recruited by the Government of India on the recommendation of the Union Public Service Commission. Fresh recruits to the IFS are trained at the Foreign Service Institute (FSI) after a brief foundation course at the Lal Bahadur Shastri National Academy of Administration, Mussoorie.[8]
Contents
1 History
2 Selection
3 Training
4 Functions
5 Career and rank structure
6 Major concerns and Reforms
6.1 Foreign Service cadre discrimination
7 Notable IFS Officers
8 References
9 External links
History[edit]
South Block The HQ of Ministry of External Affairs, Prime Minister's Office and Defence Ministry in New Delhi
Negotiating exercises like this are routine and vital part of Indian diplomats' job profile. Here, President Obama and Prime Minister Modi are with their diplomats in an expanded bilateral meeting at Hyderabad House, New Delhi.
On 13 September 1783, the board of directors of the East India Company passed a resolution at Fort William, Calcutta (now Kolkata), to create a department, which could help "relieve the pressure" on the Warren Hastings administration in conducting its "secret and political business."[1] Although established by the Company, the Indian Foreign Department conducted business with foreign European powers.[1] From the very beginning, a distinction was maintained between the foreign and political functions of the Foreign Department; relations with all "Asiatic powers" (including native princely states) were treated as political, while relations with European powers were treated as foreign.[9]
In 1843, the Governor-General of India, Edward Law, 1st Earl of Ellenborough carried out administrative reforms, organizing the Secretariat of the Government into four departments: Foreign, Home, Finance, and Military. Each was headed by a secretary-level officer. The Foreign Department Secretary was entrusted with the "conduct of all correspondence belonging to the external and internal diplomatic relations of the government."[1]
The Government of India Act 1935 attempted to delineate more clearly functions of the foreign and political wings of the Foreign Department, it was soon realized that it was administratively imperative to completely bifurcate the department. Consequently, the External Affairs Department was set up separately under the direct charge of the Governor-General.
The idea of establishing a separate diplomatic service to handle the external activities of the Government of India originated from a note dated 30 September 1944, recorded by Lieutenant-General T. J. Hutton, the Secretary of the Planning and Development Department.[1] When this note was referred to the Department of External Affairs for comments, Olaf Caroe, the Foreign Secretary, recorded his comments in an exhaustive note detailing the scope, composition and functions of the proposed service. Caroe pointed out that as India emerged as autonomous, it was imperative to build up a system of representation abroad that would be in complete harmony with the objectives of the future government.[1]
On 9 October 1946,[10] on the eve of Indian independence, the Indian government established the Indian Foreign Service for India's diplomatic, consular and commercial representation overseas. With independence, there was a near-complete transition of the Foreign and Political Department into what then became the new Ministry of External Affairs and Commonwealth Relations.
Selection[edit]
An Indian Diplomatic Passport and an Official Passport. As opposed to deep blue passport issued to ordinary Indian citizens the diplomatic passport is Maroon Coloured with Golden 'Diplomatic Passport' engraved on it and Hindi equivalent
In 1948, the first group of Indian Foreign Service officers recruited under the combined Civil Services Examination administered by the Union Public Service Commission joined the service.[11] This exam is still used to select new foreign service officers.
The Civil Services Examination is used for recruitment for the Indian Foreign Service. The entire selection process lasts for about 12 months. Only a rank among toppers guarantees an IFS selection— an acceptance rate of 0.02 percent and is known to be the 'heaven borne service'.
In recent years, the intake into the Indian Foreign Service has averaged between 25-30 persons annually. The present cadre strength of the service stands at approximately 600 officers manning around 162 Indian missions and posts abroad and the various posts in the Ministry at home(Defence,Finance,Home,etc.)
Training[edit]
On acceptance to the Foreign Service, new entrants undergo significant training,which is considered to be one of the most challenging and longest service trainings in the govt. of India and nearly takes more than 3 years to graduate from. The entrants undergo a probationary period (and are referred to as Officer Trainees) Training begins at the Lal Bahadur Shastri National Academy of Administration in Mussoorie, where members of many elite Indian civil services are trained.[1]
After completing a 15-week training at the Lal Bahadur Shastri National Academy of Administration, the probationers join the Foreign Service Institute in New Delhi for a more intensive training in a host of subjects important to diplomacy, including international relations theory, military diplomacy,trade, India's Foreign Policy, History, International Law, diplomatic practice, hospitality, protocol and administration. They also go on attachments with different government bodies and defence(Army,Navy,Air Force,CAPF) establishments and undertake tours both in India and abroad. The entire training programme lasts for a period of 36 months.[1]
Upon the completion of the training programme at the Institute, the officer is assigned a compulsory foreign language (CFL). After a brief period of desk attachment in the Ministry of External Affairs, at the rank of Assistant Secretary, the officer is posted to an Indian diplomatic mission abroad where her/his CFL is the native language. There the officer undergoes language training and is expected to develop proficiency in the CFL and pass an examination before being allowed to continue in the service.[1]
Functions[edit]
Then Indian Ambassador to the United States, Nirupama Rao, in a meeting with then U.S. Secretary of State, Hillary Clinton, in Washington, D.C., 2012
Indian High Commission in Canberra
As a career diplomat, the Foreign Service Officer is required to project India’s interests, both at home and abroad on a wide variety of issues. These include bilateral political and economic cooperation, trade and investment promotion, cultural interaction, press and media liaison as well as a whole host of multilateral issues.[1]
The functions of an Indian diplomat may be summarized as:[1]
Representing India in his/her Embassies, High Commissions, Consulates, and Permanent Missions to multilateral organizations like UN;
Protecting India’s national interests in the country of his/her posting;
Promoting friendly relations with the receiving state as also its people, including NRI/PIOs;
Reporting accurately on developments in the country of posting which are likely to influence the formulation of India’s policies;
Negotiating agreements on various issues with the authorities of the receiving state; and
Extending consular facilities to foreigners and Indian nationals abroad.
At home[1]
Ministry of External Affairs is responsible for all aspects of external relations. Territorial divisions deal with bilateral political and economic work while functional divisions look after policy planning, multilateral organizations, regional groupings, legal matters, disarmament, protocol, consular, Indian Diaspora, press and publicity, administration and other aspects.
Career and rank structure[edit]
The hierarchy in foreign service
At an embassy: in ascending order of rank
Third Secretary (entry level)
Second Secretary (promotion upon being confirmed in service)
First Secretary
Counsellor
Minister
Deputy Chief of Mission/Deputy High Commissioner/Deputy Permanent Representative
Ambassador/High Commissioner/Permanent Representative
At the Ministry of External Affairs: in ascending order of rank
Assistant Secretary/Under Secretary
Deputy Secretary
Director
Joint Secretary
Additional Secretary
Secretary
Foreign Secretary of India (India's Top Diplomat, Administrative Head of the Indian Foreign Service & Foreign Service Board)
Major concerns and Reforms[edit]
See also: Devyani Khobragade incident
In 2012, media reports showed that a foreign service officer was fined US$1.5 million[12][13] for engaging in slavery [12] by United States District Court for the Southern District of New York[12] and was also found denying visa on the basis of homosexuality.[14][15]
Shashi Tharoor, currently the Chairman of the Parliamentary Standing Committee on External Affairs,[16][17] has presented 12th report[18] for expanding and building the numbers, quality and capacity of India's diplomats.[19][20]
Foreign Service cadre discrimination[edit]
There is in total a pool of 2,700 personnel holding diplomatic rank that serve in overseas missions and at headquarters. Of these only a minority of about 770 are IFS officers, the senior cadre of Indian diplomacy, which is primarily drawn from recruitment through the Civil Services Examination. The breakdown of other cadres and personnel include 252 Grade-I officers of the IFS(B), 33 of the Interpreters Cadre, 24 of the Legal and Treaties Cadre, 635 Attaches, 540 diplomatic officers from the secretarial staff and 310 diplomatic officers from other Ministries.[2]
IFS (B) is the feeder cadre which ranks below the IFS (A) and recruits members through a separate entrance exam and after a period of 8 years are appointed and absorbed into the service.[21] Below the IFS (B) are the stenographers who provide secretarial support to both the IFS (A) and IFS (B) but especially the senior cadre.[22]
The relations between the cadres and secretarial personnel have been marked by territorial grievance and rivalry, becoming at times heated enough to spill into the public sphere.[21] A common grievance among IFS (A) officers is the practice of antedating the appointment of IFS (B) officers 8 years before the date of their actual promotion.[21] This puts the IFS (B) officers, who are seen as less prestigious, ahead for promotions of IFS (A) officers who directly entered the service before them.[21] In 2013, 6 IFS (A) officers went as far as to lodge a complaint, against their foreign secretary as well as eight IFS (B) officers named as respondents, with the Central Administrative Tribunal (CAT) for clogging the promotion pipeline and leading to "demotivation and demoralisation among direct recruit officers".[21]
IFS (B) officers have also complained of discrimination against them by IFS (A) officers. A Facebook group purportedly voicing the objections of IFS (B) officers sprung up in 2016 when IFS (B) officer Tajinder Singh, Second Secretary in the Indian embassy in Lisbon died of an apparent suicide.[23] The Facebook group alleged that Singh was treated unfairly because he was forced to yield his choice assignment in Washington DC after serving in a hardship posting in Damascus.[23] He was forced to give up his choice assignment for Lisbon because of alleged "discrimination and professional challenges from IFS (A) officers in the ministry".[23]
IFS (B) officers themselves have an acrimonious rivalry with the secretarial personnel or stenographers who are perceived to be lower in prestige than the IFS (B) officers but have a closer working relationship with IFS (A) officers, giving the stenographers at times promotion opportunities ahead of IFS (B) officers. This rivalry was brought to the fore when a stenographer was appointed as Indian ambassador to North Korea in 2012. Within a week of the appointment IFS (B) officers vociferously protested. Three different associations representing IFS (B) officers came together to write a single complaint to the Prime Minister’s Office and the external affairs minister expressing their “utter disappointment” and requesting a review of the appointment.[22]
Notable IFS Officers[edit]
C. B. Muthamma
Sardar K. M. Panikkar
Triloki Nath Kaul
Brajesh Mishra
K. R. Narayanan
J N Dixit
Natwar Singh
Mani Shankar Aiyar
Gopalaswami Parthasarathy
Mohammad Hamid Ansari
Hardeep Singh Puri
Nirupama Rao
Sujatha Singh
S Jaishankar
Syed Akbaruddin
Vikas Swarup
T. P. Sreenivasan
Arundhati Ghose
References[edit]
^ Jump up to: a b c d e f g h i j k l m n "MEA - About MEA : Indian Foreign Service". www.mea.gov.in. Retrieved 2 April 2018.
Jump up ^ Complete Civil Service Schedule of the Civil Services Group A of India." Civil Service Group A - Government of Indiaof the Central Civil Services Group B of India]." Central Civil Service Group B - Government of India 1 January 2011.
Jump up ^ "Examination Notice no. 06/2017-CSP" (PDF). Union Public Service Commission. February 22, 2017. Retrieved August 19, 2017.
Jump up ^ http://www.constitution.org/cons/india/shed07.htm
Jump up ^ "Singla appointed PS to PM Narendra Modi". hindustantimes.com. 20 July 2014. Retrieved 2 April 2018.
^ Jump up to: a b Bagchi, Indrani. "IFS officials building their own traditions". Times of India. Retrieved 10 April 2014.
Jump up ^ "Indian Foreign Service". Retrieved 10 April 2014.
Jump up ^ "Foreign Service Institute". meafsi.gov.in. Retrieved 2 April 2018.
Jump up ^ "Sorry for the inconvenience". meaindia.nic.in. Retrieved 2 April 2018.
Jump up ^ "The Indian Foreign Service:Then & Now", Indian Foreign Affairs Journal: Vol. 2, No. 2, April–June 2007
Jump up ^ http://upsc.gov.in/exams/notifications/2014/csp/CSP%202014%20English.pdf
^ Jump up to: a b c "US judge: Pay $1.5 m to maid of Indian diplomat for ill treatment". The Indian Express. Retrieved 21 December 2016.
Jump up ^ "US court asks Indian diplomat to pay $1.5m to 'tortured' maid". The Times of India. Retrieved 21 December 2016.
Jump up ^ "IFS officer denies visa to spouse of gay American diplomat, moved out". The Indian Express. Retrieved 20 January 2017.
Jump up ^ "IFS officer refuses visa to gay diplomat's spouse, transferred". Firstpost. Retrieved 20 January 2017.
Jump up ^ "Chairperson of Committees - Lok Sabha". Lok Sabha. Retrieved 7 June 2016.
Jump up ^ "Department Related Parliamentary Standing Committees (LS)". Rajya Sabha. Retrieved 24 March 2016.
Jump up ^ "Twelfth Report, Standing Committee on External Affairs: IFS cadre" (PDF). Lok Sabha. Retrieved 21 December 2016.
Jump up ^ "If Shashi Tharoor's panel has its way, India's diplomatic corps could grow in quantity and quality". Firstpost. Retrieved 21 December 2016.
Jump up ^ "Fill in IFS cadre gap, Parliament committee to Government". The Economic Times. Retrieved 21 December 2016.
^ Jump up to: a b c d e Mitra, Devirupa (November 3, 2013). "The class war in Foreign Service". New Indian Express.
^ Jump up to: a b "From steno to ambassador". New Indian Express. May 27, 2012.
^ Jump up to: a b c "MEA facing unrest among junior IFS-B officers". Indian Mandarins. July 1, 2016.
25. http://www.indianembassy.ru/index.php/home/departments-officers
External links[edit]
Official website within the Ministry of External Affairs
Official website of Foreign Service Institute India
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