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Originally published In Press as doi:10.1074/jbc.M509822200 on December 16, 2005

J. Biol. Chem., Vol. 281, Issue 7, 3926-3935, February 17, 2006
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Naturally Occurring Mutations in Human Mitochondrial Pre-tRNASer(UCN) Can Affect the Transfer Ribonuclease Z Cleavage Site, Processing Kinetics, and Substrate Secondary Structure*

Hua Yan1, Neela Zareen2, and Louis Levinger3

From the York College of The City University of New York, Jamaica, New York 11451

tRNAs are transcribed as precursors with a 5' end leader and a 3' end trailer. The 5' end leader is processed by RNase P, and in most organisms in all three kingdoms, transfer ribonuclease (tRNase) Z can endonucleolytically remove the 3' end trailer. Long (L) and short (S) forms of the tRNase Z gene are present in the human genome. tRNase ZL processes a nuclear-encoded pre-tRNA ~1600-fold more efficiently than tRNase ZS and is predicted to have a strong mitochondrial transport signal. tRNase ZL could, thus, process both nuclear- and mitochondrially encoded pre-tRNAs. More than 150 pathogenesis-associated mutations have been found in the mitochondrial genome, most of them in the 22 mitochondrially encoded tRNAs. All the mutations investigated in human mitochondrial tRNASer(UCN) affect processing efficiency, and some affect the cleavage site and secondary structure. These changes could affect tRNase Z processing of mutant pre-tRNAs, perhaps contributing to mitochondrial disease.


Received for publication, September 7, 2005 , and in revised form, December 16, 2005.

* This work was supported by National Institutes of Health Grant SO6GM08153 and a Professional Staff Congress City University of New York grant for research support. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Present address: Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029.

2 Present address: Dept. of Biology, Fairchild Center, Columbia University, NY, New York 10027.

3 To whom correspondence should be addressed: Dept. of Natural Sciences/Biology, York College of The City University of New York, 94-20 Guy R. Brewer Blvd., Jamaica, NY 11451. Tel.: 718-262-2704; Fax: 718-262-2652; E-mail: louie{at}york.cuny.edu.


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