RGD Reference Report - Modulation of exosome-mediated mRNA turnover by interaction of GTP-binding protein 1 (GTPBP1) with its target mRNAs.

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Modulation of exosome-mediated mRNA turnover by interaction of GTP-binding protein 1 (GTPBP1) with its target mRNAs.
Authors:	Woo, KC Kim, TD Lee, KH Kim, DY Kim, S Lee, HR Kang, HJ Chung, SJ Senju, S Nishimura, Y Kim, KT
Citation:	Woo KC, etal., FASEB J. 2011 Aug;25(8):2757-69. doi: 10.1096/fj.10-178715. Epub 2011 Apr 22.
RGD ID:	8553842
Pubmed:	PMID:21515746 (View Abstract at PubMed)
DOI:	DOI:10.1096/fj.10-178715 (Journal Full-text)
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-alpha 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.

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Biological Process

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Gtpbp1	Rat	GTP metabolic process	involved_in	IDA		PMID:21515746	UniProt
Gtpbp1	Rat	positive regulation of mRNA catabolic process	involved_in	IDA		PMID:21515746	UniProt

Cellular Component

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Gtpbp1	Rat	cytoplasmic exosome (RNase complex)	part_of	IDA		PMID:21515746	UniProt
Gtpbp1	Rat	cytosol	located_in	IDA		PMID:21515746	UniProt

Molecular Function

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Gtpbp1	Rat	GTPase activity	enables	IDA		PMID:21515746	UniProt

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Genes (Rattus norvegicus)

Gtpbp1 (GTP binding protein 1)

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Modulation of exosome-mediated mRNA turnover by interaction of GTP-binding protein 1 (GTPBP1) with its target mRNAs.