publication . Article . 2011

Modelling reveals kinetic advantages of co-transcriptional splicing.

Stuart Aitken; Ross D Alexander; Jean D Beggs;
Open Access
  • Published: 01 Oct 2011 Journal: PLoS Computational Biology, volume 7, page e1002215 (eissn: 1553-7358, Copyright policy)
  • Publisher: Public Library of Science (PLoS)
  • Country: United Kingdom
Abstract
Author Summary The coding information for the synthesis of proteins in mammalian cells is first transcribed from DNA to messenger RNA (mRNA), before being translated from mRNA to protein. Each step is complex, and subject to regulation. Certain sequences of DNA must be skipped in order to generate a functional protein, and these sequences, known as introns, are removed from the mRNA by the process of splicing. Splicing is well understood in terms of the proteins and complexes that are involved, but the rates of reactions, and models for the splicing pathways, have not yet been established. We present a model of splicing in yeast that accounts for the possibiliti...
Subjects
free text keywords: /dk/atira/pure/subjectarea/asjc/2300/2303, /dk/atira/pure/subjectarea/asjc/2800/2804, /dk/atira/pure/subjectarea/asjc/1100/1105, /dk/atira/pure/subjectarea/asjc/1300/1311, /dk/atira/pure/subjectarea/asjc/2600/2611, /dk/atira/pure/subjectarea/asjc/1700/1703, /dk/atira/pure/subjectarea/asjc/1300/1312, Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience, RNA splicing, Prp24, Exonic splicing enhancer, Bioinformatics, Biology, Intron, Splicing factor, Alternative splicing, Minigene, Polypyrimidine tract, Research Article, Computational Biology, Molecular Genetics, Gene Expression, Biophysic Al Simulations, RNA processing, Systems Biology, Biology (General), QH301-705.5
Related Organizations
Funded by
WT
Project
  • Funder: Wellcome Trust (WT)
,
RCUK| Centre for Systems Biology at Edinburgh
Project
  • Funder: Research Council UK (RCUK)
  • Project Code: BB/D019621/1
  • Funding stream: BBSRC
47 references, page 1 of 4

Wahl, MC, Will, CL, Lührmann, R. The spliceosome: Design principles of a dynamic RNP machine.. Cell. 2009; 136: 701-718 [OpenAIRE] [PubMed]

Brow, DA. Allosteric cascade of spliceosome activation.. Annu Rev Genet. 2002; 36: 333-360 [OpenAIRE] [PubMed]

Smith, DJ, Query, CC, Konarska, MM. “nought may endure but mutability”: Spliceosome dynamics and the regulation of splicing.. Mol Cell. 2008; 30: 657-666 [OpenAIRE] [PubMed]

Liu, L, Query, CC, Konarska, MM. Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing.. Nat Struct Mol Biol. 2008; 14: 519-526

Query, CC, Konarska, MM. Suppression of multiple substrate mutations by spliceosomal prp8 alleles suggests functional correlations with ribosomal ambiguity mutants.. Mol Cell. 2004; 14: 343-354 [OpenAIRE] [PubMed]

Reed, R. Coupling transcription, splicing and mRNA export.. Curr Opin Cell Biol. 2003; 15: 326-331 [PubMed]

Kornblihtt, AR, De La Mata, M, Fededa, JP, Munoz, MJ, Nogues, G. Multiple links between transcription and splicing.. RNA. 2004; 10: 1489-1498 [OpenAIRE] [PubMed]

Listerman, I, Sapra, AK, Neugebauer, KM. Cotranscriptional coupling of splicing factor recruitment and precursor messenger RNA splicing in mammalian cells.. Nat Struct Mol Biol. 2006; 13: 815-822 [OpenAIRE] [PubMed]

Alexander, R, Beggs, J. Cross-talk in transcription, splicing and chromatin: who makes the first call?. Biochem Soc Trans. 2010; 38: 1251-1256 [PubMed]

Alexander, RD, Innocente, SA, Barrass, JD, Beggs, JD. Splicing-dependent RNA polymerase pausing in yeast.. Mol Cell. 2010; 40: 582-593 [OpenAIRE] [PubMed]

Carrillo Oesterreich, F, Preibisch, S, Neugebauer, KM. Global analysis of nascent RNA reveals transcriptional pausing in terminal exons.. Mol Cell. 2010; 40: 571-581 [OpenAIRE] [PubMed]

Mapendano, CK, Lykke-Andersen, S, Kjems, J, Bertrand, E, Jensen, TH. Crosstalk between mRNA 3′ end processing andtranscription initiation.. Mol Cell. 2010; 40: 410-422 [OpenAIRE] [PubMed]

Darzacq, X, Singer, RH, Shav-Tal, Y. Dynamics of transcription and mRNA export.. Curr Opin Cell Biol. 2005; 17: 332-339 [OpenAIRE] [PubMed]

Pikielny, CW, Rosbach, M. mRNA splicing efficiency in yeast and the contribution of nonconserved sequences.. Cell. 1985; 41: 119-126 [PubMed]

Hicks, MJ, Yang, CR, Kotlajich, MV, Hertel, KJ. Linking splicing to Pol II transcription stabilizes pre-mRNAs and inuences splicing patterns.. PLoS Biol. 2006; 4: e147 [OpenAIRE] [PubMed]

47 references, page 1 of 4
Abstract
Author Summary The coding information for the synthesis of proteins in mammalian cells is first transcribed from DNA to messenger RNA (mRNA), before being translated from mRNA to protein. Each step is complex, and subject to regulation. Certain sequences of DNA must be skipped in order to generate a functional protein, and these sequences, known as introns, are removed from the mRNA by the process of splicing. Splicing is well understood in terms of the proteins and complexes that are involved, but the rates of reactions, and models for the splicing pathways, have not yet been established. We present a model of splicing in yeast that accounts for the possibiliti...
Subjects
free text keywords: /dk/atira/pure/subjectarea/asjc/2300/2303, /dk/atira/pure/subjectarea/asjc/2800/2804, /dk/atira/pure/subjectarea/asjc/1100/1105, /dk/atira/pure/subjectarea/asjc/1300/1311, /dk/atira/pure/subjectarea/asjc/2600/2611, /dk/atira/pure/subjectarea/asjc/1700/1703, /dk/atira/pure/subjectarea/asjc/1300/1312, Ecology, Modelling and Simulation, Computational Theory and Mathematics, Genetics, Ecology, Evolution, Behavior and Systematics, Molecular Biology, Cellular and Molecular Neuroscience, RNA splicing, Prp24, Exonic splicing enhancer, Bioinformatics, Biology, Intron, Splicing factor, Alternative splicing, Minigene, Polypyrimidine tract, Research Article, Computational Biology, Molecular Genetics, Gene Expression, Biophysic Al Simulations, RNA processing, Systems Biology, Biology (General), QH301-705.5
Related Organizations
Funded by
WT
Project
  • Funder: Wellcome Trust (WT)
,
RCUK| Centre for Systems Biology at Edinburgh
Project
  • Funder: Research Council UK (RCUK)
  • Project Code: BB/D019621/1
  • Funding stream: BBSRC
47 references, page 1 of 4

Wahl, MC, Will, CL, Lührmann, R. The spliceosome: Design principles of a dynamic RNP machine.. Cell. 2009; 136: 701-718 [OpenAIRE] [PubMed]

Brow, DA. Allosteric cascade of spliceosome activation.. Annu Rev Genet. 2002; 36: 333-360 [OpenAIRE] [PubMed]

Smith, DJ, Query, CC, Konarska, MM. “nought may endure but mutability”: Spliceosome dynamics and the regulation of splicing.. Mol Cell. 2008; 30: 657-666 [OpenAIRE] [PubMed]

Liu, L, Query, CC, Konarska, MM. Opposing classes of prp8 alleles modulate the transition between the catalytic steps of pre-mRNA splicing.. Nat Struct Mol Biol. 2008; 14: 519-526

Query, CC, Konarska, MM. Suppression of multiple substrate mutations by spliceosomal prp8 alleles suggests functional correlations with ribosomal ambiguity mutants.. Mol Cell. 2004; 14: 343-354 [OpenAIRE] [PubMed]

Reed, R. Coupling transcription, splicing and mRNA export.. Curr Opin Cell Biol. 2003; 15: 326-331 [PubMed]

Kornblihtt, AR, De La Mata, M, Fededa, JP, Munoz, MJ, Nogues, G. Multiple links between transcription and splicing.. RNA. 2004; 10: 1489-1498 [OpenAIRE] [PubMed]

Listerman, I, Sapra, AK, Neugebauer, KM. Cotranscriptional coupling of splicing factor recruitment and precursor messenger RNA splicing in mammalian cells.. Nat Struct Mol Biol. 2006; 13: 815-822 [OpenAIRE] [PubMed]

Alexander, R, Beggs, J. Cross-talk in transcription, splicing and chromatin: who makes the first call?. Biochem Soc Trans. 2010; 38: 1251-1256 [PubMed]

Alexander, RD, Innocente, SA, Barrass, JD, Beggs, JD. Splicing-dependent RNA polymerase pausing in yeast.. Mol Cell. 2010; 40: 582-593 [OpenAIRE] [PubMed]

Carrillo Oesterreich, F, Preibisch, S, Neugebauer, KM. Global analysis of nascent RNA reveals transcriptional pausing in terminal exons.. Mol Cell. 2010; 40: 571-581 [OpenAIRE] [PubMed]

Mapendano, CK, Lykke-Andersen, S, Kjems, J, Bertrand, E, Jensen, TH. Crosstalk between mRNA 3′ end processing andtranscription initiation.. Mol Cell. 2010; 40: 410-422 [OpenAIRE] [PubMed]

Darzacq, X, Singer, RH, Shav-Tal, Y. Dynamics of transcription and mRNA export.. Curr Opin Cell Biol. 2005; 17: 332-339 [OpenAIRE] [PubMed]

Pikielny, CW, Rosbach, M. mRNA splicing efficiency in yeast and the contribution of nonconserved sequences.. Cell. 1985; 41: 119-126 [PubMed]

Hicks, MJ, Yang, CR, Kotlajich, MV, Hertel, KJ. Linking splicing to Pol II transcription stabilizes pre-mRNAs and inuences splicing patterns.. PLoS Biol. 2006; 4: e147 [OpenAIRE] [PubMed]

47 references, page 1 of 4
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