title: Modulation of exosome-mediated mRNA turnover by interaction of GTP-binding protein 1 (GTPBP1) with its target mRNAs.
abstract: Eukaryotic mRNA turnover is among most critical mechanisms that affect mRNA abundance and are regulated by mRNA-binding proteins and the cytoplasmic exosome. A functional protein, guanosine-triphosphate-binding protein 1 (GTPBP1), which associates with both the exosome and target mRNAs, was identified. The overexpression of GTPBP1 accelerated the target mRNA decay, whereas the reduction of the GTPBP1 expression with RNA interference stabilized the target mRNA. GTPBP1 has a putative guanosine-triphosphate (GTP)-binding domain, which is found in members of the G-protein family and Ski7p, a well-known core factor of the exosome-mediated mRNA turnover pathway in yeast. Analyses of protein interactions and mRNA decay demonstrated that GTPBP1 modulates mRNA degradation via GTP-binding-dependent target loading. Moreover, GTPBP1-knockout models displayed multiple mRNA decay defects, including elevated nocturnal levels of Aanat mRNA in pineal glands, and retarded degradation of TNF-α mRNA in lipopolysaccharide-treated splenocytes. The results of this study suggest that GTPBP1 is a regulator and adaptor of the exosome-mediated mRNA turnover pathway.
authors.affiliation: Department of Life Science, Division of Molecular and Life Science, Pohang University of Science and Technology, Pohang, South Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Woo
authors.forename: Tae-Don
authors.initials: TD
authors.lastname: Kim
authors.forename: Kyung-Ha
authors.initials: KH
authors.lastname: Lee
authors.forename: Do-Yeon
authors.initials: DY
authors.lastname: Kim
authors.forename: Sangjune
authors.initials: S
authors.lastname: Kim
authors.forename: Hwa-Rim
authors.initials: HR
authors.lastname: Lee
authors.forename: Hyo-Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Sang J
authors.initials: SJ
authors.lastname: Chung
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Kyong-Tai
authors.initials: KT
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D016466:CHO Cells; D002940:Circadian Rhythm / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D017931:DNA Primers / Q000235:genetics; D055354:Exosomes / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism; D057809:HEK293 Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D008954:Models, Biological; D020559:Monomeric GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010870:Pineal Gland / Q000378:metabolism; D011485:Protein Binding; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; D017931:DNA Primers; C484499:Gtpbp1 protein, mouse; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; C118668:SKI7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D020559:Monomeric GTP-Binding Proteins