title: A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery.
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.
authors.affiliation: Gene Transfer Laboratory, Istituto Nazionale per la Ricerca sul Cancro, Largo R. Benzi 10, 16132 Genoa, Italy. rgherzi@yahoo.com
authors.forename: Roberto
authors.initials: R
authors.lastname: Gherzi
authors.forename: Kyung-Yeol
authors.initials: KY
authors.lastname: Lee
authors.forename: Paola
authors.initials: P
authors.lastname: Briata
authors.forename: Daniel
authors.initials: D
authors.lastname: Wegmüller
authors.forename: Christoph
authors.initials: C
authors.lastname: Moroni
authors.forename: Michael
authors.initials: M
authors.lastname: Karin
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
mesh_terms: 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*
chemical_list: 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