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Nucleic Acids Research, 2001, Vol. 29, No. 21 4334-4340
© 2001 Oxford University Press

In vitro 3'-end endonucleolytic processing defect in a human mitochondrial tRNASer(UCN) precursor with the U7445C substitution, which causes non-syndromic deafness

Louis Levinger*, Obasanjo Jacobs and Melissa James

Natural Sciences/Biology, York College/CUNY, 94–20 Guy R. Brewer Boulevard, Jamaica, NY 11451, USA

Eukaryotic tRNAs are transcribed as precursors. A 5'-end leader and 3'-end trailer are endonucleolytically removed by RNase P and 3'-tRNase before 3'-end CCA addition, aminoacylation, nuclear export and translation. 3'-End -CC can be a 3'-tRNase anti-determinant with the ability to prevent mature tRNA from recycling through 3'-tRNase. Twenty-two tRNAs punctuate the two rRNAs and 13 mRNAs in long, bidirectional mitochondrial transcripts. Accurate mitochondrial gene expression thus depends on endonucleolytic excision of tRNAs. Various mitochondrial diseases and syndromes could arise from defective tRNA end processing. The U7445C substitution in the human mitochondrial L-strand transcript (U74C directly following the discriminator base of tRNASer(UCN)) causes non-syndromic deafness. The sequence of the precursor (G{downarrow}UCU) becomes G{downarrow}CCU, resembling a 3'-tRNase anti-determinant. We demonstrate that a tRNASer(UCN) precursor with the U7445C substitution cannot be processed in vitro by 3'-tRNase from human mitochondria. A 3'-end processing defect in this tRNA precursor could thus be responsible for mitochondrial disease.

* To whom correspondence should be addressed. Tel: +1 718 262 2704; Fax: +1 718 262 2652; Email: louie{at}york.cuny.edu


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