生物
细胞生物学
线粒体
染色质
转移RNA
核糖核酸酶P
抄写(语言学)
RNA剪接
遗传学
核糖核酸
基因
语言学
哲学
作者
Christopher Rouya,King Faisal Yambire,Mark L. Derbyshire,Hanan Alwaseem,Sohail F. Tavazoie
标识
DOI:10.1101/2023.09.21.558912
摘要
SUMMARY Efficient communication between mitochondria and the nucleus underlies homoeostatic metabolic control, though the involved mitochondrial factors and their mechanisms are poorly defined. Here, we report the surprising detection of multiple mitochondrial-derived transfer RNAs (mito-tRNAs) within the nuclei of human cells. Focused studies of nuclear-transported mito-tRNA-asparagine (mtAsn) revealed that its cognate charging enzyme (NARS2) is also present in the nucleus. MtAsn promoted interaction of NARS2 with histone deacetylase 2 (HDAC2), and repressed HDAC2 association with specific chromatin loci. Perturbation of this axis using antisense oligonucleotides promoted nucleotide biogenesis and enhanced breast cancer growth, and RNA and nascent transcript sequencing demonstrated specific alterations in the transcription of nuclear genes. These findings uncover nucleic-acid mediated communication between two organelles and the existence of a machinery for nuclear gene regulation by a mito-tRNA that restricts tumor growth through metabolic control. Highlights Multiple mitochondrial-derived tRNAs are detected in human cell nuclei MtAsn promotes binding between NARS2 and HDAC2 Metabolic alterations driven by mtAsn impact cell proliferation MtAsn inhibition releases HDAC2 to bind and transcriptionally regulate multiple nuclear genes
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