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PMID: 16640457 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Linking splicing to Pol II transcription stabilizes pre-mRNAs and influences splicing patterns.

PLoS biology ·Vol. 4 ·No. 6 ·2006-06-00 ·Pages e147

Hicks MJ, Yang CR, Kotlajich MV, Hertel KJ

Abstract

RNA processing is carried out in close proximity to the site of transcription, suggesting a regulatory link between transcription and pre-mRNA splicing. Using an in vitro transcription/splicing assay, we demonstrate that an association of RNA polymerase II (Pol II) transcription and pre-mRNA splicing is required for efficient gene expression. Pol II-synthesized RNAs containing functional splice sites are protected from nuclear degradation, presumably because the local concentration of the splicing machinery is sufficiently high to ensure its association over interactions with nucleases. Furthermore, the process of transcription influences alternative splicing of newly synthesized pre-mRNAs. Because other RNA polymerases do not provide similar protection from nucleases, and their RNA products display altered splicing patterns, the link between transcription and RNA processing is RNA Pol II-specific. We propose that the connection between transcription by Pol II and pre-mRNA splicing guarantees an extended half-life and proper processing of nascent pre-mRNAs.

MeSH Terms
DNA-Directed RNA Polymerases/physiology Globins/genetics HeLa Cells Humans Kinetics Models, Genetic Plasmids/genetics RNA Polymerase II/metabolism RNA Precursors/metabolism RNA Splice Sites/physiology RNA Splicing/physiology RNA Stability RNA, Messenger/metabolism Spliceosomes/physiology Transcription, Genetic Viral Proteins/physiology
Chemicals
RNA Precursors RNA Splice Sites RNA, Messenger Viral Proteins Globins RNA Polymerase II bacteriophage T7 RNA polymerase DNA-Directed RNA Polymerases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hicks Martin J
Department of Microbiology and Molecular Genetics, University of California Irvine, Irvine, California, USA.
Yang Chin-Rang
Kotlajich Matthew V
Hertel Klemens J
References (51)
51 references, click to expand
  1. The architecture of pre-mRNAs affects mechanisms of splice-site pairing.
    Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16176-81 PMID: 16260721
  2. Transcriptional activators differ in their abilities to control alternative splicing.
    J Biol Chem. 2002 Nov 8;277(45):43110-4 PMID: 12221105
  3. Effects of RNA secondary structure on alternative splicing of pre-mRNA: is folding limited to a region behind the transcribing RNA polymerase?
    Cell. 1988 Jul 29;54(3):393-401 PMID: 2840206
  4. On the importance of being co-transcriptional.
    J Cell Sci. 2002 Oct 15;115(Pt 20):3865-71 PMID: 12244124
  5. Correction of SMN2 Pre-mRNA splicing by antisense U7 small nuclear RNAs.
    Mol Ther. 2005 Dec;12(6):1013-22 PMID: 16226920
  6. Distinct roles for CTD Ser-2 and Ser-5 phosphorylation in the recruitment and allosteric activation of mammalian mRNA capping enzyme.
    Mol Cell. 1999 Mar;3(3):405-11 PMID: 10198643
  7. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex.
    Mol Cell. 2005 Jul 1;19(1):53-63 PMID: 15989964
  8. The mRNA assembly line: transcription and processing machines in the same factory.
    Curr Opin Cell Biol. 2002 Jun;14(3):336-42 PMID: 12067656
  9. U2 as well as U1 small nuclear ribonucleoproteins are involved in premessenger RNA splicing.
    Cell. 1985 Oct;42(3):737-50 PMID: 2996775
  10. Allosteric interactions between capping enzyme subunits and the RNA polymerase II carboxy-terminal domain.
    Genes Dev. 1998 Nov 15;12(22):3482-7 PMID: 9832501
  11. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
    Nucleic Acids Res. 1983 Mar 11;11(5):1475-89 PMID: 6828386
  12. Coupling of transcription with alternative splicing: RNA pol II promoters modulate SF2/ASF and 9G8 effects on an exonic splicing enhancer.
    Mol Cell. 1999 Aug;4(2):251-8 PMID: 10488340
  13. A role for exon sequences and splice-site proximity in splice-site selection.
    Cell. 1986 Aug 29;46(5):681-90 PMID: 2427200
  14. An extensive network of coupling among gene expression machines.
    Nature. 2002 Apr 4;416(6880):499-506 PMID: 11932736
  15. The guanylyltransferase domain of mammalian mRNA capping enzyme binds to the phosphorylated carboxyl-terminal domain of RNA polymerase II.
    J Biol Chem. 1998 Apr 17;273(16):9577-85 PMID: 9545288
  16. Mechanisms of alternative pre-messenger RNA splicing.
    Annu Rev Biochem. 2003;72:291-336 PMID: 12626338
  17. RNA polymerase II carboxy-terminal domain phosphorylation is required for cotranscriptional pre-mRNA splicing and 3'-end formation.
    Mol Cell Biol. 2004 Oct;24(20):8963-9 PMID: 15456870
  18. Analyzing mechanisms of alternative pre-mRNA splicing using in vitro splicing assays.
    Methods. 2005 Dec;37(4):306-13 PMID: 16314259
  19. Functional interaction of yeast pre-mRNA 3' end processing factors with RNA polymerase II.
    Mol Cell. 2002 May;9(5):1101-11 PMID: 12049745
  20. The RNA polymerase II elongation complex.
    Annu Rev Biochem. 2003;72:693-715 PMID: 12676794
  21. Coordinate regulation of transcription and splicing by steroid receptor coregulators.
    Science. 2002 Oct 11;298(5592):416-9 PMID: 12376702
  22. An enzyme mechanism language for the mathematical modeling of metabolic pathways.
    Bioinformatics. 2005 Mar;21(6):774-80 PMID: 15509612
  23. Cotranscriptional spliceosome assembly dynamics and the role of U1 snRNA:5'ss base pairing in yeast.
    Mol Cell. 2005 Jul 1;19(1):65-75 PMID: 15989965
  24. Purification of the spliceosome A-complex and its visualization by electron microscopy.
    J Biol Chem. 1995 Jun 30;270(26):15515-22 PMID: 7797545
  25. Protein diversity from alternative splicing: a challenge for bioinformatics and post-genome biology.
    Cell. 2000 Oct 27;103(3):367-70 PMID: 11081623
  26. In vivo kinetics of mRNA splicing and transport in mammalian cells.
    Mol Cell Biol. 2002 Oct;22(19):6706-18 PMID: 12215528
  27. Co-transcriptional commitment to alternative splice site selection.
    Nucleic Acids Res. 1998 Dec 15;26(24):5568-72 PMID: 9837984
  28. Alternative splicing: increasing diversity in the proteomic world.
    Trends Genet. 2001 Feb;17(2):100-7 PMID: 11173120
  29. 5'-Capping enzymes are targeted to pre-mRNA by binding to the phosphorylated carboxy-terminal domain of RNA polymerase II.
    Genes Dev. 1997 Dec 15;11(24):3306-18 PMID: 9407024
  30. Commitment to splice site pairing coincides with A complex formation.
    Mol Cell. 2004 Aug 13;15(3):477-83 PMID: 15304226
  31. Cellerator: extending a computer algebra system to include biochemical arrows for signal transduction simulations.
    Bioinformatics. 2003 Mar 22;19(5):677-8 PMID: 12651737
  32. Serine/arginine-rich protein-dependent suppression of exon skipping by exonic splicing enhancers.
    Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5002-7 PMID: 15753297
  33. A polar mechanism coordinates different regions of alternative splicing within a single gene.
    Mol Cell. 2005 Aug 5;19(3):393-404 PMID: 16061185
  34. Functional association between promoter structure and transcript alternative splicing.
    Proc Natl Acad Sci U S A. 1997 Oct 14;94(21):11456-60 PMID: 9326631
  35. Promoter binding, initiation, and elongation by bacteriophage T7 RNA polymerase. A single-molecule view of the transcription cycle.
    J Biol Chem. 2004 Jan 30;279(5):3239-44 PMID: 14597619
  36. MAZ elements alter transcription elongation and silencing of the fibroblast growth factor receptor 2 exon IIIb.
    J Biol Chem. 2004 Jul 9;279(28):29075-84 PMID: 15126509
  37. Capping, splicing, and 3' processing are independently stimulated by RNA polymerase II: different functions for different segments of the CTD.
    Genes Dev. 2001 Jul 15;15(14):1783-95 PMID: 11459828
  38. The C-terminal domain of RNA polymerase II couples mRNA processing to transcription.
    Nature. 1997 Jan 23;385(6614):357-61 PMID: 9002523
  39. Alternative pre-mRNA splicing and proteome expansion in metazoans.
    Nature. 2002 Jul 11;418(6894):236-43 PMID: 12110900
  40. The splicing factor, Prp40, binds the phosphorylated carboxyl-terminal domain of RNA polymerase II.
    J Biol Chem. 2000 Dec 22;275(51):39935-43 PMID: 10978320
  41. Predictive identification of exonic splicing enhancers in human genes.
    Science. 2002 Aug 9;297(5583):1007-13 PMID: 12114529
  42. A slow RNA polymerase II affects alternative splicing in vivo.
    Mol Cell. 2003 Aug;12(2):525-32 PMID: 14536091
  43. Topological localization of the carboxyl-terminal domain of RNA polymerase II in the initiation complex.
    J Biol Chem. 1999 Jul 9;274(28):19868-73 PMID: 10391932
  44. In vitro coupled transcription splicing.
    Methods. 2005 Dec;37(4):314-22 PMID: 16314260
  45. Integrating mRNA processing with transcription.
    Cell. 2002 Feb 22;108(4):501-12 PMID: 11909521
  46. Structural basis of transcription: RNA polymerase II at 2.8 angstrom resolution.
    Science. 2001 Jun 8;292(5523):1863-76 PMID: 11313498
  47. Promoter architecture modulates CFTR exon 9 skipping.
    J Biol Chem. 2003 Jan 17;278(3):1511-7 PMID: 12421814
  48. Phosphorylated RNA polymerase II stimulates pre-mRNA splicing.
    Genes Dev. 1999 May 15;13(10):1234-9 PMID: 10346811
  49. Regulation of alternative splicing by a transcriptional enhancer through RNA pol II elongation.
    Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8185-90 PMID: 12060763
  50. Splicing of Balbiani ring 1 gene pre-mRNA occurs simultaneously with transcription.
    Cell. 1994 Jan 14;76(1):183-92 PMID: 8287477
  51. Multiple links between transcription and splicing.
    RNA. 2004 Oct;10(10):1489-98 PMID: 15383674
Article Info
Journal
PLoS biology
Abbr.
PLoS Biol
ISSN
1545-7885
DOI
10.1371/journal.pbio.0040147
Published
2006-06-00
Epub
2006-00-02
Pages
e147
Language
English
Region
United States
NLM ID
101183755
PMCID
PMC1450099
Subset
IM
Grants
NIGMS NIH HHS · R01 GM062287 · United States
NIGMS NIH HHS · GM 68093 · United States
NIGMS NIH HHS · GM 62287 · United States
NLM NIH HHS · T15LM 07443 · United States
NLM NIH HHS · T15 LM007443 · United States
Corrections
CommentIn
PMID: 20076584
External Links
PubMed source DOI: 10.1371/journal.pbio.0040147 PMC Full Text View journal details
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