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Nuclear and cytoplasmic poly(A) binding proteins (PABPs) favor distinct transcripts and isoforms.

Authors
  • Nicholson-Shaw, Angela L1
  • Kofman, Eric R2, 3, 4
  • Yeo, Gene W2, 3, 4
  • Pasquinelli, Amy E1
  • 1 Division of Biology, University of California, San Diego, La Jolla, CA 92093, USA.
  • 2 Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • 3 UCSD Stem Cell Program, Sanford Consortium for Regenerative Medicine, La Jolla, CA 92037, USA.
  • 4 Institute for Genomic Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Type
Published Article
Journal
Nucleic Acids Research
Publisher
Oxford University Press
Publication Date
Apr 19, 2022
Identifiers
DOI: 10.1093/nar/gkac263
PMID: 35438785
Source
Medline
Language
English
License
Unknown

Abstract

The poly(A)-tail appended to the 3'-end of most eukaryotic transcripts plays a key role in their stability, nuclear transport, and translation. These roles are largely mediated by Poly(A) Binding Proteins (PABPs) that coat poly(A)-tails and interact with various proteins involved in the biogenesis and function of RNA. While it is well-established that the nuclear PABP (PABPN) binds newly synthesized poly(A)-tails and is replaced by the cytoplasmic PABP (PABPC) on transcripts exported to the cytoplasm, the distribution of transcripts for different genes or isoforms of the same gene on these PABPs has not been investigated on a genome-wide scale. Here, we analyzed the identity, splicing status, poly(A)-tail size, and translation status of RNAs co-immunoprecipitated with endogenous PABPN or PABPC in human cells. At steady state, many protein-coding and non-coding RNAs exhibit strong bias for association with PABPN or PABPC. While PABPN-enriched transcripts more often were incompletely spliced and harbored longer poly(A)-tails and PABPC-enriched RNAs had longer half-lives and higher translation efficiency, there are curious outliers. Overall, our study reveals the landscape of RNAs bound by PABPN and PABPC, providing new details that support and advance the current understanding of the roles these proteins play in poly(A)-tail synthesis, maintenance, and function. © The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.

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