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Generation of functionally distinct isoforms of PTBP3 by alternative splicing and translation initiation

By Lit-yeen Tan, Peter Whitfield, Miriam Llorian, Elisa Monzon-casanova, D. Diaz-munoz, Martin Turner and Christopher W. J. Smith

Abstract

Polypyrimidine tract binding protein (PTBP1) is a widely expressed RNA binding protein that acts as a regulator of alternative splicing and of cytoplasmic mRNA functions. Vertebrates contain two closely-related paralogs with>75 % amino acid sequence identity. Early replacement of PTBP1 by PTBP2 dur-ing neuronal differentiation causes a concerted set of splicing changes. By comparison, very little is known about the molecular functions or physiologi-cal roles of PTBP3, although its expression and con-servation throughout the vertebrates suggest a role in haematopoietic cells. To begin to understand its functions we have characterized the mRNA and pro-tein isoform repertoire of PTBP3. Combinatorial alter-native splicing events at the 5 ′ end of the gene allow for the generation of eight mRNA and three major protein isoforms. Individual mRNAs generate up to three protein isoforms via alternative translation initi-ation by re-initiation and leaky scanning using down-stream AUG codons. The N-terminally truncated PTBP3 isoforms lack nuclear localization signals and/or most of the RRM1 domain and vary in their RNA binding properties and nuclear/cytoplasmic distribution, suggesting that PTBP3 may have major post-transcriptional cytoplasmic roles. Our findings set the stage for understanding the non-redundant physiological roles of PTBP3

Year: 2015
OAI identifier: oai:CiteSeerX.psu:10.1.1.826.4387
Provided by: CiteSeerX
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