{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:49:06Z","timestamp":1790459346062,"version":"4.1.0"},"reference-count":57,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:p>Point mutations in hmtRNAs (human mitochondrial tRNAs) can cause various disorders, such as CPEO (chronic progressive external ophthalmoplegia) and MM (mitochondrial myopathy). Mitochondrial tRNALeu, especially the UUR codon isoacceptor, is recognized as a hot spot for pathogenic mtDNA point mutations. Thus far, 40 mutations have been reported in hmtRNAsLeu. In the present paper, we describe the wide range of effects of two substitutions found in the T\u03a8C arms of two hmtRNAsLeu isoacceptors. The G52A substitution, corresponding to the pathogenic G12315A mutation in tRNALeu(CUN), and G3283A in tRNALeu(UUR) exhibited structural changes in the outer corner of the tRNA shape as shown by RNase probing. These mutations also induced reductions in aminoacylation, 3\u2032-end processing and base modification processes. The main effects of the A57G substitution, corresponding to mutations A12320G in tRNALeu(CUN) and A3288G in tRNALeu(UUR), were observed on the aminoacylation activity and binding to hmEF-Tu (human mitochondrial elongation factor Tu). These observations suggest that the wide range of effects may amplify the deleterious impact on mitochondrial protein synthesis in\u00a0vivo. The findings also emphasize that an exact understanding of tRNA dysfunction is critical for the future development of therapies for mitochondrial diseases.<\/jats:p>","DOI":"10.1042\/bj20130294","type":"journal-article","created":{"date-parts":[[2013,5,2]],"date-time":"2013-05-02T13:58:57Z","timestamp":1367503137000},"page":"455-465","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Multilevel functional and structural defects induced by two pathogenic mitochondrial tRNA mutations"],"prefix":"10.1042","volume":"453","author":[{"given":"Meng","family":"Wang","sequence":"first","affiliation":[{"name":"Center for RNA Research, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, People's Republic of China"},{"name":"Architecture et R\u00e9activit\u00e9 de l\u2019ARN, Universit\u00e9 de Strasbourg, Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Mol\u00e9culaire et Cellulaire, 15 rue Ren\u00e9 Descartes, 67084 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Long","family":"Zhou","sequence":"additional","affiliation":[{"name":"Center for RNA Research, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Juan","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for RNA Research, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, Shanghai 200031, People's Republic of 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