期刊
NUCLEIC ACIDS RESEARCH
卷 47, 期 8, 页码 4240-4254出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkz129
关键词
-
资金
- Associazione Italiana per la Ricerca sul Cancro [AIRC-IG2015] [16720]
- Sapienza University of Rome [RM11715C646D693E, RP11715C644A5CCE, GA116154C8A94E3D]
- Istituto-Pasteur Italia-Fondazione Cenci Bolognetti
- European Research Council [RI-BOMYLOME_309545]
- Spanish Ministry of Economy and Competitiveness [BFU2014-55054-P, BFU2017-86970-P]
- Fundacio La Marato de TV3 [PI043296]
- Ministerio de Ciencia e Innovacion (Plan Nacional de I+D+I, Spain) [SAF2016-80639-P]
- Associazione Italiana per la Ricerca sul Cancro [AIRC-MFAG2017] [20447]
Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the onecarbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据