Home LiteratureArticle Details
PMID: 16418482 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Quantitative microarray profiling provides evidence against widespread coupling of alternative splicing with nonsense-mediated mRNA decay to control gene expression.

Genes & development ·Vol. 20 ·No. 2 ·2006-01-15 ·Pages 153-8

Pan Q, Saltzman AL, Kim YK, Misquitta C, Shai O, Maquat LE, Frey BJ, Blencowe BJ

Abstract

Sequence-based analyses have predicted that approximately 35% of mammalian alternative splicing (AS) events produce premature termination codon (PTC)-containing splice variants that are targeted by the process of nonsense-mediated mRNA decay (NMD). This led to speculation that AS may often regulate gene expression by activating NMD. Using AS microarrays, we show that PTC-containing splice variants are generally produced at uniformly low levels across diverse mammalian cells and tissues, independently of the action of NMD. Our results suggest that most PTC-introducing AS events are not under positive selection pressure and therefore may not contribute important functional roles.

MeSH Terms
Alternative Splicing Animals Codon, Nonsense/genetics,metabolism Computational Biology Gene Expression Regulation HeLa Cells Humans Mice Oligonucleotide Array Sequence Analysis Open Reading Frames RNA Helicases/metabolism RNA Stability RNA, Messenger/genetics,metabolism Trans-Activators Transfection
Chemicals
Codon, Nonsense RNA, Messenger Rent1 protein, mouse Trans-Activators RNA Helicases UPF1 protein, human
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Pan Qun
Banting and Best Department of Medical Research, University of Toronto, Ontario, M5G 1L6, Canada.
Saltzman Arneet L
Kim Yoon Ki
Misquitta Christine
Shai Ofer
Maquat Lynne E
Frey Brendan J
Blencowe Benjamin J
References (39)
39 references, click to expand
  1. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays.
    Science. 2003 Dec 19;302(5653):2141-4 PMID: 14684825
  2. Nonsense-mediated mRNA decay in mammalian cells involves decapping, deadenylating, and exonucleolytic activities.
    Mol Cell. 2003 Sep;12(3):675-87 PMID: 14527413
  3. mRNA surveillance of expressed pseudogenes in C. elegans.
    Curr Biol. 2005 May 24;15(10):963-7 PMID: 15916954
  4. Functional divergence of proteins through frameshift mutations.
    Trends Genet. 2005 Aug;21(8):428-31 PMID: 15951050
  5. Sequence conservation, relative isoform frequencies, and nonsense-mediated decay in evolutionarily conserved alternative splicing.
    Proc Natl Acad Sci U S A. 2005 Sep 6;102(36):12813-8 PMID: 16123126
  6. How prevalent is functional alternative splicing in the human genome?
    Trends Genet. 2004 Feb;20(2):68-71 PMID: 14746986
  7. An unappreciated role for RNA surveillance.
    Genome Biol. 2004;5(2):R8 PMID: 14759258
  8. Evidence for a subpopulation of conserved alternative splicing events under selection pressure for protein reading frame preservation.
    Nucleic Acids Res. 2004;32(4):1261-9 PMID: 14982953
  9. Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics.
    Nat Rev Mol Cell Biol. 2004 Feb;5(2):89-99 PMID: 15040442
  10. Nonsense-mediated mRNA decay: from vacuum cleaner to Swiss army knife.
    Genome Biol. 2004;5(4):218 PMID: 15059251
  11. Nonsense-mediated mRNA decay: terminating erroneous gene expression.
    Curr Opin Cell Biol. 2004 Jun;16(3):293-9 PMID: 15145354
  12. The evolving roles of alternative splicing.
    Curr Opin Struct Biol. 2004 Jun;14(3):273-82 PMID: 15193306
  13. Nonsense-mediated decay approaches the clinic.
    Nat Genet. 2004 Aug;36(8):801-8 PMID: 15284851
  14. Nonsense surveillance regulates expression of diverse classes of mammalian transcripts and mutes genomic noise.
    Nat Genet. 2004 Oct;36(10):1073-8 PMID: 15448691
  15. smg mutants affect the expression of alternatively spliced SR protein mRNAs in Caenorhabditis elegans.
    Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9782-5 PMID: 9275202
  16. A rule for termination-codon position within intron-containing genes: when nonsense affects RNA abundance.
    Trends Biochem Sci. 1998 Jun;23(6):198-9 PMID: 9644970
  17. A computational and experimental approach toward a priori identification of alternatively spliced exons.
    RNA. 2004 Dec;10(12):1838-44 PMID: 15525709
  18. Revealing global regulatory features of mammalian alternative splicing using a quantitative microarray platform.
    Mol Cell. 2004 Dec 22;16(6):929-41 PMID: 15610736
  19. The functional landscape of mouse gene expression.
    J Biol. 2004;3(5):21 PMID: 15588312
  20. Alternative splicing of conserved exons is frequently species-specific in human and mouse.
    Trends Genet. 2005 Feb;21(2):73-7 PMID: 15661351
  21. Mammalian Staufen1 recruits Upf1 to specific mRNA 3'UTRs so as to elicit mRNA decay.
    Cell. 2005 Jan 28;120(2):195-208 PMID: 15680326
  22. Identification and analysis of alternative splicing events conserved in human and mouse.
    Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2850-5 PMID: 15708978
  23. Nonsense-mediated RNA decay: a molecular system micromanaging individual gene activities and suppressing genomic noise.
    Bioessays. 2005 May;27(5):463-6 PMID: 15832387
  24. Mechanistic links between nonsense-mediated mRNA decay and pre-mRNA splicing in mammalian cells.
    Curr Opin Cell Biol. 2005 Jun;17(3):309-15 PMID: 15901502
  25. Alternative pre-mRNA splicing: the logic of combinatorial control.
    Trends Biochem Sci. 2000 Aug;25(8):381-8 PMID: 10916158
  26. Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability.
    Hum Mol Genet. 2001 Jan 15;10(2):99-105 PMID: 11152657
  27. Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon.
    Cell. 2000 Dec 22;103(7):1121-31 PMID: 11163187
  28. Alternative splicing: increasing diversity in the proteomic world.
    Trends Genet. 2001 Feb;17(2):100-7 PMID: 11173120
  29. SC35 autoregulates its expression by promoting splicing events that destabilize its mRNAs.
    EMBO J. 2001 Apr 2;20(7):1785-96 PMID: 11285241
  30. Role of the nonsense-mediated decay factor hUpf3 in the splicing-dependent exon-exon junction complex.
    Science. 2001 Sep 7;293(5536):1832-6 PMID: 11546873
  31. Alternative splicing: multiple control mechanisms and involvement in human disease.
    Trends Genet. 2002 Apr;18(4):186-93 PMID: 11932019
  32. Listening to silence and understanding nonsense: exonic mutations that affect splicing.
    Nat Rev Genet. 2002 Apr;3(4):285-98 PMID: 11967553
  33. The exon junction complex is detected on CBP80-bound but not eIF4E-bound mRNA in mammalian cells: dynamics of mRNP remodeling.
    EMBO J. 2002 Jul 1;21(13):3536-45 PMID: 12093754
  34. Evidence for the widespread coupling of alternative splicing and nonsense-mediated mRNA decay in humans.
    Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):189-92 PMID: 12502788
  35. Y14 and hUpf3b form an NMD-activating complex.
    Mol Cell. 2003 Apr;11(4):939-49 PMID: 12718880
  36. Alternative splicing in the human, mouse and rat genomes is associated with an increased frequency of exon creation and/or loss.
    Nat Genet. 2003 Jun;34(2):177-80 PMID: 12730695
  37. Widespread predicted nonsense-mediated mRNA decay of alternatively-spliced transcripts of human normal and disease genes.
    Bioinformatics. 2003;19 Suppl 1:i118-21 PMID: 12855447
  38. Mechanisms of alternative pre-messenger RNA splicing.
    Annu Rev Biochem. 2003;72:291-336 PMID: 12626338
  39. Autoregulation of polypyrimidine tract binding protein by alternative splicing leading to nonsense-mediated decay.
    Mol Cell. 2004 Jan 16;13(1):91-100 PMID: 14731397
Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2006-01-15
Pages
153-8
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1356107
Subset
IM
Grants
NIGMS NIH HHS · R01 GM059614 · United States
NIGMS NIH HHS · GM059614 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com