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Mol Cell Biol February 1, 2015; 35 (4): 758-68.

A posttranscriptional mechanism that controls Ptbp1 abundance in the Xenopus epidermis.

Méreau A , Anquetil V , Lerivray H , Viet J , Schirmer C , Audic Y , Legagneux V , Hardy S , Paillard L .

The output of alternative splicing depends on the cooperative or antagonistic activities of several RNA-binding proteins (RBPs), like Ptbp1 and Esrp1 in Xenopus. Fine-tuning of the RBP abundance is therefore of prime importance to achieve tissue- or cell-specific splicing patterns. Here, we addressed the mechanisms leading to the high expression of the ptbp1 gene, which encodes Ptbp1, in Xenopus epidermis. Two splice isoforms of ptbp1 mRNA differ by the presence of an alternative exon 11, and only the isoform including exon 11 can be translated to a full-length protein. In vivo minigene assays revealed that the nonproductive isoform was predominantly produced. Knockdown experiments demonstrated that Esrp1, which is specific to the epidermis, strongly stimulated the expression of ptbp1 by favoring the productive isoform. Consequently, knocking down esrp1 phenocopied ptbp1 inactivation. Conversely, Ptbp1 repressed the expression of its own gene by favoring the nonproductive isoform. Hence, a complex posttranscriptional mechanism controls Ptbp1 abundance in Xenopus epidermis: skipping of exon 11 is the default splicing pattern, but Esrp1 stimulates ptbp1 expression by favoring the inclusion of exon 11 up to a level that is limited by Ptbp1 itself. These results decipher a posttranscriptional mechanism that achieves various abundances of the ubiquitous RBP Ptbp1 in different tissues.

PubMed ID: 25512611
PMC ID: PMC4301716
Article link: Mol Cell Biol

Species referenced: Xenopus laevis
Genes referenced: eef1a1 endog esrp1 pcna ptbp1 ptbp2 rbm4 tpm1
Antibodies: Esrp1 Ab1 Pcna Ab5 V5 Ab1
Morpholinos: esrp1 MO1 ptbp1 MO1

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References [+] :
Anquetil, Polypyrimidine tract binding protein prevents activity of an intronic regulatory element that promotes usage of a composite 3'-terminal exon. 2009, Pubmed, Xenbase