title: Scaffold function of long non-coding RNA HOTAIR in protein ubiquitination.
abstract: 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.
authors: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA.
authors: Je-Hyun
authors: JH
authors: Yoon
authors: Kotb
authors: K
authors: Abdelmohsen
authors: Jiyoung
authors: J
authors: Kim
authors: Xiaoling
authors: X
authors: Yang
authors: Jennifer L
authors: JL
authors: Martindale
authors: Kumiko
authors: K
authors: Tominaga-Yamanaka
authors: Elizabeth J
authors: EJ
authors: White
authors: Arturo V
authors: AV
authors: Orjalo
authors: John L
authors: JL
authors: Rinn
authors: Stefan G
authors: SG
authors: Kreft
authors: Gerald M
authors: GM
authors: Wilson
authors: Myriam
authors: M
authors: Gorospe
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism; D000067696:Ataxin-1; D000067528:Ataxins; D016922:Cellular Senescence / Q000235:genetics; D051959:ELAV Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D039381:RNA Cap-Binding Proteins / Q000378:metabolism; D020871:RNA Stability; D062085:RNA, Long Noncoding / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C466422:AGO2 protein, human; C000593749:ATXN1 protein, human; D060565:Argonaute Proteins; D000067696:Ataxin-1; D000067528:Ataxins; D051959:ELAV Proteins; C561566:HOTAIR long untranslated RNA, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D039381:RNA Cap-Binding Proteins; D062085:RNA, Long Noncoding; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C114090:SNUPN protein, human; C476989:DZIP3 protein, human; D044767:Ubiquitin-Protein Ligases