Somatic and Germline MicroRNAs Form Distinct Silencing Complexes to Regulate Their Target mRNAs Differently

Dev Cell. 2018 Oct 22;47(2):239-247.e4. doi: 10.1016/j.devcel.2018.08.022. Epub 2018 Sep 20.

Abstract

Animal germ cells possess a specific post-transcriptional regulatory context allowing the storage of maternal transcripts in the oocyte until their translation at a specific point in early development. As key regulators of gene expression, miRNAs repress translation mainly through mRNA destabilization. Thus, germline miRNAs likely use distinct ways to regulate their targets. Here, we use C. elegans to compare miRNA function within germline and somatic tissues. We show that the same miRNA displays tissue-specific gene regulatory mechanisms. While translational repression occurs in both tissues, targeted mRNAs are instead stabilized in the germline. Comparative analyses of miRNA silencing complexes (miRISC) demonstrate that their composition differs from germline to soma. We show that germline miRNA targets preferentially localize to perinuclear regions adjacent to P granules, and their repression is dependent on the core P granule component GLH-1. Together, our findings reveal the existence of different miRISC in animals that affect targeted mRNAs distinctively.

Keywords: Argonaute; GLH-1; GW182; Germ granule; VASA; mRNA protection; maternal mRNA; miRISC.

Publication types

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

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Gene Expression Regulation / genetics*
  • Gene Silencing / physiology*
  • Germ Cells / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oocytes / metabolism
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / metabolism

Substances

  • Argonaute Proteins
  • Caenorhabditis elegans Proteins
  • MicroRNAs
  • RNA, Messenger
  • RNA-Binding Proteins