Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Dev Dyn. 2005 Jul;233(3):783-93.

Dynamic balance between activation and repression regulates pre-mRNA alternative splicing during heart development.

Author information

  • 1Department of Pathology, Baylor College of Medicine, Houston, Texas 77030, USA.

Abstract

Cardiac troponin T (cTNT) exon 5 splicing is developmentally regulated such that it is included in embryonic but not adult heart. CUG-BP and ETR-3-like factor (CELF) proteins promote exon inclusion, whereas polypyrimidine tract binding protein (PTB) and muscleblind-like (MBNL) proteins repress inclusion. In this study, we addressed what happens to these regulatory proteins during heart development to shift the regulatory balance of cTNT alternative splicing. Using dominant-negative proteins, we found that both CELF and PTB activities are required for appropriate splicing in cardiomyocytes. Two CELF proteins, CUG-BP and ETR-3, are nuclear and cytoplasmic in embryonic heart but are down-regulated in adult heart concomitant with loss of exon inclusion. In contrast, PTB and MBNL1 are expressed throughout heart development. The patterns of cTNT splicing and expression of its regulatory factors are conserved between mouse and chicken. Thus, alternative splicing is determined by a balance between positive and negative regulation, and modulation of expression levels of auxiliary splicing regulators may drive developmental splicing changes. ETR-3 and CUG-BP proteins are also down-regulated in other tissues during development, suggesting that CELF proteins play a broad role in developmental splicing regulation.

PMID:
15830352
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Write to the Help Desk