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Alternative polyadenylation can regulate post-translational membrane localization.

Mithun Mitra1, Elizabeth L Johnson2, Hilary A Coller1

  • 1Department of Molecular, Cell and Developmental Biology, UCLA, and Department of Biological Chemistry, David Geffen School of Medicine, Los Angeles, CA 90095.

Trends in Cell & Molecular Biology
|March 4, 2016
PubMed
Summary
This summary is machine-generated.

Alternative polyadenylation (APA) can alter protein localization and function by influencing RNA transcripts. This study reveals APA affects CD47 protein localization via RNA-mediated recruitment, not mRNA trafficking.

Keywords:
CD47HuRRAC1SETalternative polyadenylationplasma membrane

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Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • Alternative polyadenylation (APA) generates multiple transcript isoforms from a single gene.
  • APA typically occurs in 3' untranslated regions (UTRs), often not affecting protein sequence.
  • However, APA can impact transcript stability, translatability, and subcellular localization.

Purpose of the Study:

  • To investigate the functional consequences of APA in 3' UTRs.
  • To elucidate the mechanism by which APA influences protein localization.
  • To determine if this APA-mediated regulation is specific to CD47 or a broader phenomenon.

Main Methods:

  • Analysis of alternative polyadenylation in the CD47 gene.
  • Experimental manipulation of polyadenylation site selection.
  • Assessment of protein localization using cell biology techniques.
  • Investigation of the underlying molecular mechanisms, distinguishing mRNA trafficking from RNA-mediated protein recruitment.

Main Results:

  • Alternative polyadenylation of CD47 transcripts, despite identical protein sequences, leads to differential protein localization.
  • Proximal polyadenylation site usage results in endoplasmic reticulum localization, while distal site usage leads to plasma membrane localization.
  • This localization control is mediated by RNA-recruiting proteins to the CD47 transcript, not by differential mRNA trafficking.
  • Similar APA-mediated regulation was observed for other transmembrane proteins.

Conclusions:

  • Alternative polyadenylation site selection in 3' UTRs can directly influence protein localization and function, even without altering the protein sequence.
  • The mRNA transcript can act as a scaffold to recruit proteins, thereby regulating the fate and localization of the encoded protein.
  • This highlights a novel layer of post-transcriptional gene regulation with significant implications for cellular function.