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

Genetics. 2018 Apr;208(4):1513-1522. doi: 10.1534/genetics.118.300791. Epub 2018 Feb 21.

Abstract

Several in vitro studies have suggested that canonical microRNA (miRNA) biogenesis requires the DICER cofactors TARBP2 and PRKRA for processing of pre-miRNAs to mature miRNAs. To investigate the roles of TARBP2 and PRKRA in miRNA biogenesis in vivo, and to determine possible functional redundancy, we first compared the phenotypes of Tarbp2 and Prkra single and double mutants. In contrast to Dicer -/- embryos, which die by embryonic day 7.5 (E7.5), single Tarbp2 -/- and Prkra -/- mice survive beyond E7.5 and either die perinatally or survive and exhibit cranial/facial abnormalities, respectively. In contrast, only a few Tarbp2 -/- ; Prkra -/- double mutants survived beyond E12.5, suggesting genetic redundancy between Tarbp2 and Prkra during embryonic development. Sequencing of miRNAs from single-mutant embryos at E15.5 revealed changes in abundance and isomiR type in Tarbp2 -/- , but not Prkra -/- , embryos, demonstrating that TARBP2, but not PRKRA, functions in miRNA biogenesis of a subclass of miRNAs, and suggesting that functional redundancy between TARBP2 and PRKRA does not involve miRNA biogenesis.

Keywords: DICER; PACT; PRKRA; TARBP2; miRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Embryonic Development / genetics*
  • Female
  • Gene Expression Regulation, Developmental*
  • Genes, Lethal
  • Genetic Association Studies
  • Genotype
  • Male
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Phenotype
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism

Substances

  • MicroRNAs
  • Prkra protein, mouse
  • RNA-Binding Proteins
  • trans-activation responsive RNA-binding protein