The CELF family of RNA binding proteins is implicated in cell-specific and developmentally regulated alternative splicing.

Mol Cell Biol 2001 Feb;21(4):1285-96

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

Alternative splicing of cardiac troponin T (cTNT) exon 5 undergoes a developmentally regulated switch such that exon inclusion predominates in embryonic, but not adult, striated muscle. We previously described four muscle-specific splicing enhancers (MSEs) within introns flanking exon 5 in chicken cTNT that are both necessary and sufficient for exon inclusion in embryonic muscle. We also demonstrated that CUG-binding protein (CUG-BP) binds a conserved CUG motif within a human cTNT MSE and positively regulates MSE-dependent exon inclusion. Here we report that CUG-BP is one of a novel family of developmentally regulated RNA binding proteins that includes embryonically lethal abnormal vision-type RNA binding protein 3 (ETR-3). This family, which we call CELF proteins for CUG-BP- and ETR-3-like factors, specifically bound MSE-containing RNAs in vitro and activated MSE-dependent exon inclusion of cTNT minigenes in vivo. The expression of two CELF proteins is highly restricted to brain. CUG-BP, ETR-3, and CELF4 are more broadly expressed, and expression is developmentally regulated in striated muscle and brain. Changes in the level of expression and isoforms of ETR-3 in two different developmental systems correlated with regulated changes in cTNT splicing. A switch from cTNT exon skipping to inclusion tightly correlated with induction of ETR-3 protein expression during differentiation of C2C12 myoblasts. During heart development, the switch in cTNT splicing correlated with a transition in ETR-3 protein isoforms. We propose that ETR-3 is a major regulator of cTNT alternative splicing and that the CELF family plays an important regulatory role in cell-specific alternative splicing during normal development and disease.

Download full-text PDF

Source
http://dx.doi.org/10.1128/MCB.21.4.1285-1296.2001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC99581PMC
February 2001
11 Reads

Publication Analysis

Top Keywords

exon inclusion
16
alternative splicing
16
developmentally regulated
16
rna binding
12
striated muscle
8
ctnt
8
mse-dependent exon
8
ctnt exon
8
binding proteins
8
switch ctnt
8
celf family
8
ctnt splicing
8
celf proteins
8
etr-3 protein
8
exon
7
splicing
7
etr-3
6
regulated
5
inclusion
5
heart development
4

Similar Publications