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A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery
Journal
Molecular cell
Volume
14
Number
5
Pages / Article-Number
571-83
Keywords
3' Untranslated Regions/physiology; Amino Acid Motifs/physiology; Binding Sites/physiology; Exoribonucleases/genetics/metabolism; Heterogeneous-Nuclear Ribonucleoprotein D/genetics/*metabolism; Humans; Protein Binding/physiology; Protein Structure; Tertiary/physiology; RNA Stability/*physiology; RNA; Messenger/genetics/*metabolism; RNA-Binding Proteins/genetics/*metabolism; TATA-Binding Protein Associated Factors/genetics/metabolism; Trans-Activators/genetics/*metabolism
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.
