Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA.
Nat Commun. 2013;4:2939. doi: 10.1038/ncomms3939.
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.
尽管哺乳动物长链非编码 (lnc)RNA 以调节转录而闻名，但它们对 mRNA 剪接、稳定性和翻译的转录后影响正在显现。在这里，我们报告了 lncRNA HOTAIR 的一个翻译后功能，作为泛素介导的蛋白水解的诱导剂。HOTAIR 与具有 RNA 结合结构域的 E3 泛素连接酶 Dzip3 和 Mex3b 以及它们各自的泛素化底物 Ataxin-1 和 Snurportin-1 结合。通过这种方式，HOTAIR 促进了 Dzip3 对 Ataxin-1 和 Mex3b 对 Snurportin-1 的泛素化，并加速了它们的降解。HOTAIR 水平在衰老细胞中高度上调，导致靶蛋白 Ataxin-1 和 Snurportin-1 的快速降解，并防止过早衰老。这些结果揭示了 lncRNA HOTAIR 作为蛋白质泛素化平台的作用。
