DUSP11 - An RNA phosphatase that regulates host and viral non-coding RNAs in mammalian cells

RNA Biol. 2017 Nov 2;14(11):1457-1465. doi: 10.1080/15476286.2017.1306169. Epub 2017 Apr 17.

Abstract

Dual-specificity phosphatase 11 (DUSP11) is a conserved protein tyrosine phosphatase (PTP) in metazoans. The cellular substrates and physiologic activities of DUSP11 remain largely unknown. In nematodes, DUSP11 is required for normal development and RNA interference against endogenous RNAs (endo-RNAi) via molecular mechanisms that are not well understood. However, mammals lack analogous endo-RNAi pathways and consequently, a role for DUSP11 in mammalian RNA silencing was unanticipated. Recent work from our laboratory demonstrated that DUSP11 activity alters the silencing potential of noncanonical viral miRNAs in mammalian cells. Our studies further uncovered direct cellular substrates of DUSP11 and suggest that DUSP11 is part of regulatory pathway that controls the abundance of select triphosphorylated noncoding RNAs. Here, we highlight recent findings and present new data that advance understanding of mammalian DUSP11 during gene silencing and discuss the emerging biological activities of DUSP11 in mammalian cells.

Keywords: Argonaute; BLV; DUSP11; PIR-1; RNAi; VA RNA; dicer; miRNA; miRNA biogenesis; triphosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / genetics
  • Argonaute Proteins / metabolism
  • Caenorhabditis elegans
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • Dual-Specificity Phosphatases / genetics*
  • Dual-Specificity Phosphatases / metabolism
  • Gene Expression Regulation
  • Host-Pathogen Interactions / genetics*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • RNA Polymerase III / genetics
  • RNA Polymerase III / metabolism
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • RNA, Viral / genetics*
  • RNA, Viral / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism
  • Signal Transduction
  • Viruses / genetics
  • Viruses / metabolism

Substances

  • Argonaute Proteins
  • DGCR8 protein, human
  • MicroRNAs
  • RNA, Small Interfering
  • RNA, Viral
  • RNA-Binding Proteins
  • RNA-Induced Silencing Complex
  • RNA Polymerase II
  • RNA Polymerase III
  • DICER1 protein, human
  • DROSHA protein, human
  • Ribonuclease III
  • DUSP11 protein, human
  • Dual-Specificity Phosphatases
  • DEAD-box RNA Helicases