title: Direct binding of Ataxin-2 to distinct elements in 3' UTRs promotes mRNA stability and protein expression.
abstract: It has been proposed that Ataxin-2, a member of the like-Sm (LSm) protein family, participates in the regulation of RNA metabolism through interaction with PABPC1. However, the exact biological mechanism and in vivo targets remain unknown. Here, we report that Ataxin-2 binds directly to RNAs in a PABPC1-independent manner. High-throughput sequencing of Ataxin-2-bound RNAs prepared by PAR-CLIP revealed that Ataxin-2 binds predominantly to uridine-rich elements, including well-characterized cis-regulatory AU-rich elements, in the 3' UTRs of target mRNAs. Gene expression analysis after Ataxin-2 depletion or overexpression revealed that Ataxin-2 stabilizes target mRNAs and increases the abundance of the corresponding proteins. A tethering assay demonstrated that Ataxin-2 elicits this effect by direct interaction with mRNAs. We also found that disease-associated polyglutamine expansion downregulates the physiological activity of Ataxin-2. These findings suggest that Ataxin-2 is an RNA-binding protein that targets cis-regulatory elements in 3' UTRs to stabilize a subset of mRNAs and increase protein expression.
authors: Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Moe
authors: M
authors: Yokoshi
authors: Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Quan
authors: Q
authors: Li
authors: Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Munetaka
authors: M
authors: Yamamoto
authors: Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Hitomi
authors: H
authors: Okada
authors: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-1 Kashiwanoha, Kashiwa, Chiba 277-8561, Japan.
authors: Yutaka
authors: Y
authors: Suzuki
authors: Department of RNA Biology and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: ykawahara@rna.med.osaka-u.ac.jp.
authors: Yukio
authors: Y
authors: Kawahara
mesh_terms: D020413:3' Untranslated Regions; D000067528:Ataxins; D001665:Binding Sites; D051959:ELAV Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D063990:Gene Ontology; D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000067528:Ataxins; D051959:ELAV Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D012333:RNA, Messenger; C097188:polyglutamine