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Frac-seq reveals isoform-specific recruitment to polyribosomes.

Authors
  • T, Sterne-Weiler
  • Rt, Martinez-Nunez
  • Jm, Howard
  • I, Cvitovik
  • S, Katzman
  • Ma, Tariq
  • N, Pourmand
  • Jeremy Sanford
Type
Published Article
Journal
Genome Research
Publisher
Cold Spring Harbor Laboratory
Volume
23
Issue
10
Pages
1615–1623
Identifiers
DOI: 10.1101/gr.148585.112
Source
UCSC Bioinformatics biomedical-ucsc
License
Unknown

Abstract

Pre-mRNA splicing is required for the accurate expression of virtually all human protein coding genes. However, splicing also plays important roles in coordinating subsequent steps of pre-mRNA processing such as polyadenylation and mRNA export. Here, we test the hypothesis that nuclear pre-mRNA processing influences the polyribosome association of alternative mRNA isoforms. By comparing isoform ratios in cytoplasmic and polyribosomal extracts, we determined that the alternative products of ∼30% (597/1954) of mRNA processing events are differentially partitioned between these subcellular fractions. Many of the events exhibiting isoform-specific polyribosome association are highly conserved across mammalian genomes, underscoring their possible biological importance. We find that differences in polyribosome association may be explained, at least in part by the observation that alternative splicing alters the cis-regulatory landscape of mRNAs isoforms. For example, inclusion or exclusion of upstream open reading frames (uORFs) in the 5 UTR as well as Alu-elements and microRNA target sites in the 3 UTR have a strong influence on polyribosome association of alternative mRNA isoforms. Taken together, our data demonstrate for the first time the potential link between alternative splicing and translational control of the resultant mRNA isoforms.

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