Functional Redundancy of DICER Cofactors TARBP2 and PRKRA During Murine Embryogenesis Does Not Involve miRNA

Sri Ramulu N Pullagura1,2, Bill Buaas1, Nichelle Gray1

  • 1The Jackson Laboratory, Bar Harbor, Maine 04609.

Genetics
|February 23, 2018
PubMed

Insights

MicroRNA (miRNA) processing in vivo requires TARBP2 and PRKRA. While single mutants survive, double mutants show developmental defects, indicating genetic redundancy. However, this redundancy doesn't involve miRNA biogenesis.

Area of Science:

  • Molecular Biology
  • Developmental Biology
  • Genetics

Background:

  • Canonical microRNA (miRNA) biogenesis involves DICER cofactors TARBP2 and PRKRA for pre-miRNA processing in vitro.
  • The in vivo roles and potential functional redundancy of TARBP2 and PRKRA in miRNA biogenesis remain unclear.

Purpose of the Study:

  • To investigate the in vivo functions of TARBP2 and PRKRA in miRNA biogenesis.
  • To determine the extent of functional redundancy between TARBP2 and PRKRA during embryonic development.

Main Methods:

  • Generation and analysis of Tarbp2 and Prkra single and double mutant mice.
  • Phenotypic characterization of mutant embryos at various developmental stages.
  • miRNA sequencing in single-mutant embryos to assess changes in abundance and isomiR profiles.

Main Results:

  • Single Tarbp2 and Prkra mutant mice exhibit distinct phenotypes, with some surviving postnatally.
  • Tarbp2;Prkra double mutants show significantly reduced survival rates beyond embryonic day 12.5, suggesting genetic redundancy.
  • miRNA sequencing revealed altered miRNA abundance and isomiR types in Tarbp2 mutant embryos, but not in Prkra mutants, indicating TARBP2's role in miRNA biogenesis for a subset of miRNAs.

Conclusions:

  • TARBP2, but not PRKRA, plays a direct role in the biogenesis of a subclass of miRNAs in vivo.
  • Genetic redundancy between TARBP2 and PRKRA during embryonic development does not appear to be mediated through miRNA biogenesis.
  • These findings highlight distinct and overlapping functions of TARBP2 and PRKRA in mouse development and miRNA pathways.

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