Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Cell. 2004 Jan 16;13(1):91-100.

Autoregulation of polypyrimidine tract binding protein by alternative splicing leading to nonsense-mediated decay.

Author information

  • 1Department of Biochemistry, 80 Tennis Court Road, University of Cambridge, Cambridge CB2 1GA, United Kingdom.

Abstract

Polypyrimdine tract binding protein (PTB) is a regulator of alternative splicing, mRNA 3' end formation, mRNA stability and localization, and IRES-mediated translation. Transient overexpression of PTB can influence alternative splicing, sometimes resulting in nonphysiological splicing patterns. Here, we show that alternative skipping of PTB exon 11 leads to an mRNA that is removed by NMD and that this pathway consumes at least 20% of the PTB mRNA in HeLa cells. We also show that exon 11 skipping is itself promoted by PTB in a negative feedback loop. This autoregulation may serve both to prevent disruptively high levels of PTB expression and to restore nuclear levels when PTB is mobilized to the cytoplasm. Our findings suggest that alternative splicing can act not only to generate protein isoform diversity but also to quantitatively control gene expression and complement recent bioinformatic analyses, indicating a high prevalence of human alternative splicing leading to NMD.

PMID:
14731397
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk