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Nucleic Acids Res. 2015 Jun 23;43(11):5586-600. doi: 10.1093/nar/gkv429. Epub 2015 May 4.

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

Author information

1
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
2
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, CB22 3AT, UK.
3
Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, CB22 3AT, UK.
4
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK cwjs1@cam.ac.uk.

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 during neuronal differentiation causes a concerted set of splicing changes. By comparison, very little is known about the molecular functions or physiological roles of PTBP3, although its expression and conservation throughout the vertebrates suggest a role in haematopoietic cells. To begin to understand its functions we have characterized the mRNA and protein isoform repertoire of PTBP3. Combinatorial alternative 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 initiation by re-initiation and leaky scanning using downstream 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.

PMID:
25940628
PMCID:
PMC4477659
DOI:
10.1093/nar/gkv429
[Indexed for MEDLINE]
Free PMC Article

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