A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery

Roberto Gherzi, Kyung Yeol Lee, Paola Briata, Daniel Wegmüller, Christoph Moroni, Michael Karin, Ching Yi Chen

Research output: Contribution to journalArticle


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.

Original languageEnglish
Pages (from-to)571-583
Number of pages13
JournalMolecular Cell
Issue number5
Publication statusPublished - Jun 4 2004


ASJC Scopus subject areas

  • Molecular Biology

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