title: Alternative polyadenylation diversifies post-transcriptional regulation by selective RNA-protein interactions.
abstract: Recent research has uncovered extensive variability in the boundaries of transcript isoforms, yet the functional consequences of this variation remain largely unexplored. Here, we systematically discriminate between the molecular phenotypes of overlapping coding and non-coding transcriptional events from each genic locus using a novel genome-wide, nucleotide-resolution technique to quantify the half-lives of 3' transcript isoforms in yeast. Our results reveal widespread differences in stability among isoforms for hundreds of genes in a single condition, and that variation of even a single nucleotide in the 3' untranslated region (UTR) can affect transcript stability. While previous instances of negative associations between 3' UTR length and transcript stability have been reported, here, we find that shorter isoforms are not necessarily more stable. We demonstrate the role of RNA-protein interactions in conditioning isoform-specific stability, showing that PUF3 binds and destabilizes specific polyadenylation isoforms. Our findings indicate that although the functional elements of a gene are encoded in DNA sequence, the selective incorporation of these elements into RNA through transcript boundary variation allows a single gene to have diverse functional consequences.
authors.affiliation: European Molecular Biology Laboratory (EMBL), Genome Biology Unit, Heidelberg, Germany.
authors.forename: Ishaan
authors.initials: I
authors.lastname: Gupta
authors.forename: Sandra
authors.initials: S
authors.lastname: Clauder-Münster
authors.forename: Bernd
authors.initials: B
authors.lastname: Klaus
authors.forename: Aino I
authors.initials: AI
authors.lastname: Järvelin
authors.forename: Raeka S
authors.initials: RS
authors.lastname: Aiyar
authors.forename: Vladimir
authors.initials: V
authors.lastname: Benes
authors.forename: Stefan
authors.initials: S
authors.lastname: Wilkening
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Huber
authors.forename: Vicent
authors.initials: V
authors.lastname: Pelechano
authors.forename: Lars M
authors.initials: LM
authors.lastname: Steinmetz
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D026723:Polyadenylation; D012323:RNA Processing, Post-Transcriptional / Q000235:genetics*; D020871:RNA Stability / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C510155:PUF3 protein, S cerevisiae; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins