学术报告
题目：Mitochondrial RNA Import
报告人：Geng Wang, Ph.D.
Department of Chemistry and Biochemistry, University of California, Los Angeles
时间：Tuesday 11:00 a.m., December 6
地点：生命科学学院411会议室
Mutations in the human mitochondrial genome are implicated in neuromuscular diseases, metabolic defects, and aging. An efficient and simple mechanism for neutralizing deleterious mitochondrial DNA (mtDNA) alterations has unfortunately remained elusive. RNA import into mammalian mitochondria is considered essential for replication, transcription, and translation of the mitochondrial genome but the pathway(s) and factors that control this import are poorly understood. We identified the first mammalian mitochondrial RNA import factor PNPASE (polynucleotide phosphorylase) and a 20-ribonucleotide stem-loop sequence from the import substrates as the import signal. When appended to a non-imported RNA, the import signal directs the import of the resultant RNA fusion transcript into human mitochondria. The methodology is effective for both non-coding RNAs, such as tRNAs, and mRNAs, and can be adapted to import wild-type RNA transcripts to complement the mitochondrial DNA mutations. In vivo, functional defects in mitochondrial RNA (mtRNA) translation and cell respiration were reversed in two human disease lines, providing an exciting, general approach for overcoming mitochondrial genetic disorders.
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