Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination

被引：357

作者：

Yoon, Je-Hyun ^{[1
]}

Abdelmohsen, Kotb ^{[1
]}

Kim, Jiyoung ^{[1
]}

Yang, Xiaoling ^{[1
]}

Martindale, Jennifer L. ^{[1
]}

Tominaga-Yamanaka, Kumiko ^{[1
]}

White, Elizabeth J. ^{[2
,3
]}

Orjalo, Arturo V. ^{[4
]}

Rinn, John L. ^{[5
]}

Kreft, Stefan G. ^{[6
]}

Wilson, Gerald M. ^{[2
,3
]}

Gorospe, Myriam ^{[1
]}

机构：

[1] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[2] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA

[3] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA

[4] Biosearch Technol Inc, Novato, CA 94949 USA

[5] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[6] Univ Constance, Dept Biol, D-78457 Constance, Germany

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

BINDING PROTEIN; REPLICATIVE SENESCENCE; INTERACTION NETWORK; HUR; PHOSPHORYLATION; EXPRESSION; ATAXIN-1; DECAY; DIFFERENTIATION; IDENTIFICATION;

D O I：

10.1038/ncomms3939

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Although mammalian long non-coding (lnc) RNAs are best known for modulating transcription, their post-transcriptional influence on mRNA splicing, stability and translation is emerging. Here we report a post-translational function for the lncRNA HOTAIR as an inducer of ubiquitin-mediated proteolysis. HOTAIR associates with E3 ubiquitin ligases bearing RNA-binding domains, Dzip3 and Mex3b, as well as with their respective ubiquitination substrates, Ataxin-1 and Snurportin-1. In this manner, HOTAIR facilitates the ubiquitination of Ataxin-1 by Dzip3 and Snurportin-1 by Mex3b in cells and in vitro, and accelerates their degradation. HOTAIR levels are highly upregulated in senescent cells, causing rapid decay of targets Ataxin-1 and Snurportin-1, and preventing premature senescence. These results uncover a role for a lncRNA, HOTAIR, as a platform for protein ubiquitination.

引用

页数：14

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