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The hypertension-associated m.4401A&gt;G mutation resided at a spacer between mitochondrial tRNAMet and tRNAGln genes. An in vitro processing experiment revealed that the m.4401A&gt;G mutation caused 59% and 69% decreases in the 5\u2032 end processing efficiency of tRNAGln and tRNAMet precursors, catalyzed by RNase P, respectively. Using human umbilical vein endothelial cells-derived cybrids, we demonstrated that the m.4401A&gt;G mutation caused the decreases of all 8 tRNAs and ND6 and increases of longer and uncleaved precursors from the Light-strand transcript. Conversely, the m.4401A&gt;G mutation yielded the reduced levels of tRNAMet level but did not change the levels of other 13 tRNAs, 12 mRNAs including ND1, 12S rRNA and 16S rRNA from the Heavy-strand transcript. These implicated the asymmetrical processing mechanisms of H-strand and L-strand polycistronic transcripts. The tRNA processing defects play the determined roles in the impairing mitochondrial translation, respiratory deficiency, diminishing membrane potential, increasing production of reactive oxygen species and altering autophagy. Furthermore, the m.4401A&gt;G mutation altered the angiogenesis, evidenced by aberrant wound regeneration and weaken tube formation in mutant cybrids. Our findings provide new insights into the pathophysiology of hypertension arising from mitochondrial tRNA processing defects.<\/jats:p>","DOI":"10.1093\/nar\/gkz742","type":"journal-article","created":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T15:37:33Z","timestamp":1566488253000},"page":"10340-10356","source":"Crossref","is-referenced-by-count":29,"title":["Hypertension-associated mitochondrial DNA 4401A&gt;G mutation caused the aberrant processing of tRNAMet, all 8 tRNAs and ND6 mRNA in the light-strand transcript"],"prefix":"10.1093","volume":"47","author":[{"given":"Xiaoxu","family":"Zhao","sequence":"first","affiliation":[{"name":"Division of Medical Genetics and Genomics, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China"},{"name":"Institute of Genetics, and Department of Human Genetics, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, 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