A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery.
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.
Gherzi
Roberto
R
Gene Transfer Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genoa, Italy. rgherzi@yahoo.com
Lee
Kyung-Yeol
KY
Briata
Paola
P
Wegmüller
Daniel
D
Moroni
Christoph
C
Karin
Michael
M
Chen
Ching-Yi
CY
D020413:3' Untranslated Regions / Q000502:physiology; D020816:Amino Acid Motifs / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D005095:Exoribonucleases / Q000235:genetics / Q000378:metabolism; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D035381:TATA-Binding Protein Associated Factors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D005095:Exoribonucleases; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D035381:TATA-Binding Protein Associated Factors; D015534:Trans-Activators; C441028:BRF1 protein, human; C000630986:HNRNPD protein, human; C105789:KHSRP protein, human