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论文题目: Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation
英文论文题目: Regulation of mitochondrial biogenesis in erythropoiesis by mTORC1-mediated protein translation
第一作者: Liu, X; Zhang, YY; Ni, M; Cao, H; Signer, RAJ; Li, D; Li, MS; Gu, ZM; Hu, ZP; Dickerson, KE; Weinberg, SE; Chandel, NS; DeBerardinis, RJ; Zhou, F; Shao, Z; Xu, JA
英文第一作者: Liu, X; Zhang, YY; Ni, M; Cao, H; Signer, RAJ; Li, D; Li, MS; Gu, ZM; Hu, ZP; Dickerson, KE; Weinberg, SE; Chandel, NS; DeBerardinis, RJ; Zhou, F; Shao, Z; Xu, JA
联系作者: Shao, Z (reprint author), Chinese Acad Sci, Key Lab Computat Biol, Collaborat Innovat Ctr Genet & Dev Biol, CAS MPG Partner Inst Computat Biol,Shanghai Inst, Shanghai 200031, Peoples R China.
英文联系作者: Shao, Z (reprint author), Chinese Acad Sci, Key Lab Computat Biol, Collaborat Innovat Ctr Genet & Dev Biol, CAS MPG Partner Inst Computat Biol,Shanghai Inst, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 19
期: 6
页码: 626-+
摘要: Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, and defective mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced to promote translation of mitochondria-associated transcripts through TOP-like motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1 specifically impairs erythropoiesis in vitro and in vivo. Our studies support a mechanism for post-transcriptional control of erythroid mitochondria and may have direct relevance to haematologic defects associated with mitochondrial diseases and ageing.
英文摘要: Advances in genomic profiling present new challenges of explaining how changes in DNA and RNA are translated into proteins linking genotype to phenotype. Here we compare the genome-scale proteomic and transcriptomic changes in human primary haematopoietic stem/progenitor cells and erythroid progenitors, and uncover pathways related to mitochondrial biogenesis enhanced through post-transcriptional regulation. Mitochondrial factors including TFAM and PHB2 are selectively regulated through protein translation during erythroid specification. Depletion of TFAM in erythroid cells alters intracellular metabolism, leading to elevated histone acetylation, deregulated gene expression, and defective mitochondria and erythropoiesis. Mechanistically, mTORC1 signalling is enhanced to promote translation of mitochondria-associated transcripts through TOP-like motifs. Genetic and pharmacological perturbation of mitochondria or mTORC1 specifically impairs erythropoiesis in vitro and in vivo. Our studies support a mechanism for post-transcriptional control of erythroid mitochondria and may have direct relevance to haematologic defects associated with mitochondrial diseases and ageing.
刊物名称: NATURE CELL BIOLOGY
英文刊物名称: NATURE CELL BIOLOGY
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 20.06
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论文类别: Article
英文论文类别: Article
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