A KH Domain RNA Binding Protein, KSRP, Promotes ARE-directed mRNA Turnover by Recruiting the Degradation Machinery

Mol Cell. 2004 Jun 4;14(5):571-83. doi: 10.1016/j.molcel.2004.05.002.

Abstract

Inherently unstable mRNAs contain AU-rich elements (AREs) in their 3' untranslated regions that act as mRNA stability determinants by interacting with ARE binding proteins (ARE-BPs). The mechanisms underlying the function of ARE and ARE-BP interactions in promoting mRNA decay are not fully understood. Here, we demonstrate that KSRP, a KH domain-containing ARE-BP, is an essential factor for ARE-directed mRNA decay. Some of the KH motifs (KHs) of KSRP directly mediate RNA binding, mRNA decay, and interactions with the exosome and poly(A) ribonuclease (PARN). The ability of KHs to promote mRNA decay correlates with their ability to bind the ARE and associate with RNA-degrading enzymes. Thus, KHs promote rapid mRNA decay by recruiting degradation machinery to ARE-containing mRNAs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3' Untranslated Regions / physiology
  • Amino Acid Motifs / physiology
  • Binding Sites / physiology
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / genetics
  • Heterogeneous-Nuclear Ribonucleoprotein D / metabolism*
  • Humans
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • RNA Stability / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • TATA-Binding Protein Associated Factors / genetics
  • TATA-Binding Protein Associated Factors / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • 3' Untranslated Regions
  • BRF1 protein, human
  • HNRPD protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • KHSRP protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • TATA-Binding Protein Associated Factors
  • Trans-Activators
  • Exoribonucleases
  • poly(A)-specific ribonuclease