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DOI | 10.1002/2016GL072305 |
mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide | |
Matsumoto, Akinobu1; Pasut, Alessandra1; Matsumoto, Masaki2; Yamashita, Riu3; Fung, Jacqueline1; Monteleone, Emanuele1,4,5; Saghatelian, Alan6; Nakayama, Keiichi I.2; Clohessy, John G.1; Pandolfi, Pier Paolo1 | |
2017-01-12 | |
发表期刊 | NATURE |
ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2017 |
卷号 | 541期号:7636页码:228-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Japan; Italy |
英文摘要 | Although long non-coding RNAs (lncRNAs) are non-protein-coding transcripts by definition, recent studies have shown that a fraction of putative small open reading frames within lncRNAs are translated(1-3). However, the biological significance of these hidden polypeptides is still unclear. Here we identify and functionally characterize a novel polypeptide encoded by the lncRNA LINC00961. This polypeptide is conserved between human and mouse, is localized to the late endosome/lysosome and interacts with the lysosomal v-ATPase to negatively regulate mTORC1 activation. This regulation of mTORC1 is specific to activation of mTORC1 by amino acid stimulation, rather than by growth factors. Hence, we termed this polypeptide 'small regulatory polypeptide of amino acid response' (SPAR). We show that the SPAR-encoding lncRNA is highly expressed in a subset of tissues and use CRISPR/Cas9 engineering to develop a SPAR-polypeptide-specific knockout mouse while maintaining expression of the host lncRNA. We find that the SPAR-encoding lncRNA is downregulated in skeletal muscle upon acute injury, and using this in vivo model we establish that SPAR downregulation enables efficient activation of mTORC1 and promotes muscle regeneration. Our data provide a mechanism by which mTORC1 activation may be finely regulated in a tissue-specific manner in response to injury, and a paradigm by which lncRNAs encoding small polypeptides can modulate general biological pathways and processes to facilitate tissue-specific requirements, consistent with their restricted and highly regulated expression profile. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000396125500043 |
WOS关键词 | AMINO-ACIDS ; RAG GTPASES ; PEPTIDES ; RAGULATOR ; REVEALS ; GENOME ; RAPTOR ; CELLS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/27894 |
专题 | 气候变化 |
作者单位 | 1.Harvard Med Sch, Canc Res Inst, Beth Israel Deaconess Canc Ctr, Dept Med & Pathol,Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA; 2.Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 8128582, Japan; 3.Tohoku Univ, Tohoku Med Megabank Org ToMMo, Dept BioBank, Sendai, Miyagi 9808573, Japan; 4.Univ Turin, Mol Biotechnol Ctr, Via Nizza 52, I-10126 Turin, Italy; 5.Univ Turin, Dept Mol Biotechnol & Hlth Sci, Via Nizza 52, I-10126 Turin, Italy; 6.Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, Helmsley Ctr Genom Med, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA |
推荐引用方式 GB/T 7714 | Matsumoto, Akinobu,Pasut, Alessandra,Matsumoto, Masaki,et al. mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide[J]. NATURE,2017,541(7636):228-+. |
APA | Matsumoto, Akinobu.,Pasut, Alessandra.,Matsumoto, Masaki.,Yamashita, Riu.,Fung, Jacqueline.,...&Pandolfi, Pier Paolo.(2017).mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide.NATURE,541(7636),228-+. |
MLA | Matsumoto, Akinobu,et al."mTORC1 and muscle regeneration are regulated by the LINC00961-encoded SPAR polypeptide".NATURE 541.7636(2017):228-+. |
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