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[[File:Abortive cycling.png|thumb|400px|Abortive cycling by [[T7 RNA polymerase]] ]]'''Abortive initiation''', also known as '''abortive transcription''', is an early process of [[Transcription (genetics)|genetic transcription]] in which [[RNA polymerase]] binds to a [[Promoter (genetics)|DNA promoter]] and enters into cycles of brief synthesis of short [[Messenger RNA |mRNA]] transcripts which are released before the transcription complex leaves the promotor. This process occurs in both [[eukaryotes]] and [[prokaryotes]]. Abortive initiation is typically studied in the T3 and [[T7 RNA polymerase]]s in [[bacteriophage]]s, and in ''[[E. coli]]''.
[[File:Abortive cycling.png|thumb|400px|Abortive cycling by [[T7 RNA polymerase]] ]]'''Abortive initiation''', also known as '''abortive transcription''', is an early process of [[Transcription (genetics)|genetic transcription]] in which [[RNA polymerase]] binds to a [[Promoter (genetics)|DNA promoter]] and enters into cycles of synthesis of short [[Messenger RNA |mRNA]] transcripts which are released before the transcription complex leaves the promotor. This process occurs in both [[eukaryotes]] and [[prokaryotes]]. Abortive initiation is typically studied in the T3 and [[T7 RNA polymerase]]s in [[bacteriophage]]s, and in ''[[E. coli]]''.


==Overall process==
==Overall process==
Line 9: Line 9:


==Mechanism==
==Mechanism==
Abortive initiation is a normal part of transcription<ref name="Goldman">{{cite journal | author=Goldman S, [[Richard H. Ebright|Ebright]] RH, Nickels B | year = 2009 | title = Direct detection of abortive RNA transcripts ''in vivo'' | url = | journal = Science | volume = 324 | issue = 5929| pages = 927–928 | doi = 10.1126/science.1169237 | pmid = 19443781 | pmc = 2718712 }}</ref>. Although RNA polymerase initially binds to the DNA promoter, these enzyme-promoter interactions do not contribute to the reluctance of RNA polymerase to cease abortive cycling and begin elongation. During this early stage of transcription, RNA polymerase enters a phase during which dissociation of the transcription complex significantly competes with the elongation process.<ref name="pmid3415967">{{cite journal| author=Martin CT, Muller DK, Coleman JE| title=Processivity in early stages of transcription by T7 RNA polymerase. | journal=Biochemistry | year= 1988 | volume= 27 | issue= 11 | pages= 3966-74 | pmid=3415967 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3415967 }} </ref>
Abortive initiation occurs both ''in vitro'' and ''in vivo''<ref name="Goldman">{{cite journal | author=Goldman S, [[Richard H. Ebright|Ebright]] RH, Nickels B | year = 2009 | title = Direct detection of abortive RNA transcripts ''in vivo'' | url = | journal = Science | volume = 324 | issue = 5929| pages = 927–928 | doi = 10.1126/science.1169237 | pmid = 19443781 | pmc = 2718712 }}</ref>. After each nucleotide-addition step in initial transcription, RNA polymerase, stochastically, can proceed on the pathway toward promoter escape (productive initiation) or can release the RNA product and revert to the RNA polymerase-promoter open complex (abortive initiation).<ref name="pmid3415967">{{cite journal| author=Martin CT, Muller DK, Coleman JE| title=Processivity in early stages of transcription by T7 RNA polymerase. | journal=Biochemistry | year= 1988 | volume= 27 | issue= 11 | pages= 3966-74 | pmid=3415967 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3415967 }} </ref>


===DNA scrunching===
===DNA scrunching===
[[File:DNA scrunching.png|thumb|360px|DNA scrunching mechanism. RNA polymerase (RNAP) pulls DNA into itself, causing the bunching up of the unwound DNA strand.]]For many years, the mechanism by which RNA polymerase moves along the DNA strand during abortive initiation remained elusive. It had been observed that RNA polymerase did not escape from the promoter during transcription initiation, so it was unknown how the enzyme could read the DNA strand to transcribe it without moving [[Upstream and downstream (DNA)|downstream]]. Within the last decade, studies have revealed that abortive initiation involves ''DNA scrunching,'' in which RNA polymerase remains stationary while it unwinds and pulls downstream DNA into the transcription complex enough to pass the nucleotides through the polymerase active site, thereby transcribing the DNA without moving. This causes the unwound DNA to bunch up within the enzyme, hence the name DNA "scrunching". Upon release of the abortive RNA, RNA polymerase ejects the accumulated DNA, returning it to its initial state.<ref name="pmid17110577" /><ref name="pmid17110578">{{cite journal| author=Kapanidis AN, Margeat E, Ho SO, Kortkhonjia E, Weiss S, Ebright RH| title=Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism. | journal=Science | year= 2006 | volume= 314 | issue= 5802 | pages= 1144-7 | pmid=17110578 | doi=10.1126/science.1131399 | pmc=2754788 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17110578 }} </ref>
[[File:DNA scrunching.png|thumb|360px|DNA scrunching mechanism. During initial transcription, RNA polymerase (RNAP) remains stationary on the promoter and unwinds and reels in downstream DNA.]] For many years, the mechanism by which RNA polymerase moves along the DNA strand during abortive initiation remained elusive. It had been observed that RNA polymerase did not escape from the promoter during transcription initiation, so it was unknown how the enzyme could read the DNA strand to transcribe it without moving [[Upstream and downstream (DNA)|downstream]]. Within the last decade, studies have revealed that abortive initiation involves ''DNA scrunching,'' in which RNA polymerase remains stationary while it unwinds and pulls downstream DNA into the transcription complex to pass the nucleotides through the polymerase active site, thereby transcribing the DNA without moving. This causes the unwound DNA to accumulate within the enzyme, hence the name DNA "scrunching". In abortive initiation, RNA polymerase re-winds and ejects the downstream portion of the unwound DNA, releasing the RNA, and reverting to the RNA polymerase-promoter open complex; in contrast, in productive initiation, RNA polymerase re-winds and ejects the upstream portion of the unwound DNA, breaking RNA polymerase-promoter interactions, escaping the promoter, and forming a transcription elongation complex<ref name="pmid17110577" /><ref name="pmid17110578">{{cite journal| author=Kapanidis AN, Margeat E, Ho SO, Kortkhonjia E, Weiss S, Ebright RH| title=Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism. | journal=Science | year= 2006 | volume= 314 | issue= 5802 | pages= 1144-7 | pmid=17110578 | doi=10.1126/science.1131399 | pmc=2754788 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17110578 }} </ref>


A 2006 paper that demonstrated the involvement of DNA scrunching in transcription initiation proposed the idea that the stress induced by DNA scrunching may be the driving force for abortive initiation and also for promoter escape and initiation of productive transcription.<ref name="pmid17110578" /> A companion paper published the same year confirmed that detectable DNA scrunching occurs in 80% of transcription cycles, and is actually estimated to be 100%, given the limitation of the ability to detect rapid scrunching (20% of scrunches have a duration of less than 1 second).<ref name="pmid17110577" />
A 2006 paper that demonstrated the involvement of DNA scrunching in initial transcription proposed the idea that the stress incurred during DNA scrunching provides the driving force for both abortive initiation and productive initiation.<ref name="pmid17110578" /> A companion paper published the same year confirmed that detectable DNA scrunching occurs in 80% of transcription cycles, and is actually estimated to be 100%, given the limitation of the ability to detect rapid scrunching (20% of scrunches have a duration of less than 1 second).<ref name="pmid17110577" />


==Function==
==Function==

Revision as of 01:06, 3 May 2014

Abortive cycling by T7 RNA polymerase

Abortive initiation, also known as abortive transcription, is an early process of genetic transcription in which RNA polymerase binds to a DNA promoter and enters into cycles of synthesis of short mRNA transcripts which are released before the transcription complex leaves the promotor. This process occurs in both eukaryotes and prokaryotes. Abortive initiation is typically studied in the T3 and T7 RNA polymerases in bacteriophages, and in E. coli.

Overall process

Abortive initiation occurs prior to promoter clearance.[1]

  1. RNA polymerase binds to promoter DNA to form an RNA polymerase-promoter closed complex
  2. RNA polymerase then unwinds one turn of DNA surrounding the transcription start site to yield an RNA polymerase-promoter open complex
  3. RNA polymerase enters into abortive cycles of synthesis and releases short RNA products (up to 10 nucleotides in length)
  4. RNA polymerase escapes the promoter and enters into the elongation step of transcription

Mechanism

Abortive initiation occurs both in vitro and in vivo[2]. After each nucleotide-addition step in initial transcription, RNA polymerase, stochastically, can proceed on the pathway toward promoter escape (productive initiation) or can release the RNA product and revert to the RNA polymerase-promoter open complex (abortive initiation).[3]

DNA scrunching

DNA scrunching mechanism. During initial transcription, RNA polymerase (RNAP) remains stationary on the promoter and unwinds and reels in downstream DNA.

For many years, the mechanism by which RNA polymerase moves along the DNA strand during abortive initiation remained elusive. It had been observed that RNA polymerase did not escape from the promoter during transcription initiation, so it was unknown how the enzyme could read the DNA strand to transcribe it without moving downstream. Within the last decade, studies have revealed that abortive initiation involves DNA scrunching, in which RNA polymerase remains stationary while it unwinds and pulls downstream DNA into the transcription complex to pass the nucleotides through the polymerase active site, thereby transcribing the DNA without moving. This causes the unwound DNA to accumulate within the enzyme, hence the name DNA "scrunching". In abortive initiation, RNA polymerase re-winds and ejects the downstream portion of the unwound DNA, releasing the RNA, and reverting to the RNA polymerase-promoter open complex; in contrast, in productive initiation, RNA polymerase re-winds and ejects the upstream portion of the unwound DNA, breaking RNA polymerase-promoter interactions, escaping the promoter, and forming a transcription elongation complex[1][4]

A 2006 paper that demonstrated the involvement of DNA scrunching in initial transcription proposed the idea that the stress incurred during DNA scrunching provides the driving force for both abortive initiation and productive initiation.[4] A companion paper published the same year confirmed that detectable DNA scrunching occurs in 80% of transcription cycles, and is actually estimated to be 100%, given the limitation of the ability to detect rapid scrunching (20% of scrunches have a duration of less than 1 second).[1]

Function

There are no widely-accepted functions for the resulting truncated RNA transcripts. However, a study in 1981 found evidence that there was a relationship between the amount of abortive transcripts produced and the time until long RNA strands are successfully produced. When RNA polymerase undergoes abortive transcription in the presence of ATP, UTP, and GTP, a complex is formed that has a much lower capacity for abortive recycling and a much higher rate of synthesis of the full-length RNA transcript.[5] A study in 2010 did find evidence supporting that these truncated transcripts inhibit termination of RNA synthesis by a RNA hairpin-dependent intrinsic terminator.[6]

See also

References

  1. ^ a b c Revyakin A, Liu C, Ebright RH, Strick TR (2006). "Abortive initiation and productive initiation by RNA polymerase involve DNA scrunching". Science. 314 (5802): 1139–43. doi:10.1126/science.1131398. PMC 2754787. PMID 17110577.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. ^ Goldman S, Ebright RH, Nickels B (2009). "Direct detection of abortive RNA transcripts in vivo". Science. 324 (5929): 927–928. doi:10.1126/science.1169237. PMC 2718712. PMID 19443781.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ Martin CT, Muller DK, Coleman JE (1988). "Processivity in early stages of transcription by T7 RNA polymerase". Biochemistry. 27 (11): 3966–74. PMID 3415967.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ a b Kapanidis AN, Margeat E, Ho SO, Kortkhonjia E, Weiss S, Ebright RH (2006). "Initial transcription by RNA polymerase proceeds through a DNA-scrunching mechanism". Science. 314 (5802): 1144–7. doi:10.1126/science.1131399. PMC 2754788. PMID 17110578.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. ^ Munson LM, Reznikoff WS (1981). "Abortive initiation and long ribonucleic acid synthesis". Biochemistry. 20 (8): 2081–5. PMID 6165380.
  6. ^ Lee S, Nguyen HM, Kang C (2010). "Tiny abortive initiation transcripts exert antitermination activity on an RNA hairpin-dependent intrinsic terminator". Nucleic Acids Res. 38 (18): 6045–53. doi:10.1093/nar/gkq450. PMC 2952870. PMID 20507918.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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