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Identification of Alternative Splicing and Polyadenylation in RNA-seq Data
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Alternative polyadenylation factors link cell cycle to migration.

Mithun Mitra1,2, Elizabeth L Johnson3, Vinay S Swamy4

  • 1Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.

Genome Biology
|October 27, 2018
PubMed
Summary

Changes in pre-mRNA processing, specifically involving cleavage and polyadenylation factors, are crucial for fibroblast migration during wound healing. Reduced levels of these factors in quiescent cells impair migration.

Keywords:
MigrationProliferationQuiescenceWound healingmRNA processing

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Wound Healing Research

Background:

  • Fibroblast activation, proliferation, and migration are key to wound healing.
  • Pre-mRNA processing changes may influence fibroblast migration during cell cycle entry.

Purpose of the Study:

  • To investigate the role of pre-mRNA processing in fibroblast migration.
  • To identify specific mRNA processing factors linking proliferation state to migration.

Main Methods:

  • RNA sequencing of quiescent and proliferating fibroblasts.
  • Analysis of transcript 3' end mapping and decay.
  • In vivo studies using mouse excisional wounds.
  • Knockdown experiments of the CstF-64 factor.

Main Results:

  • Quiescent fibroblasts show downregulated mRNA processing genes, including splicing and cleavage/polyadenylation factors.
  • Increased intron retention and longer transcripts from distal polyadenylation sites in quiescent cells.
  • Proliferating cells near wounds express higher levels of cleavage and polyadenylation factors.
  • Reduced CstF-64 levels in quiescent fibroblasts correlate with slower migration.

Conclusions:

  • Cleavage and polyadenylation factors link fibroblast proliferation state to migration.
  • These factors are critical regulators of fibroblast behavior in wound healing.