HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 19, 16828-16833, May 9, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/19/16828    most recent M213216200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tomari, Y. Articles by Ueda, T. Search for Related Content PubMed PubMed Citation Articles by Tomari, Y. Articles by Ueda, T. Social Bookmarking                      What's this?

Decreased CCA-addition in Human Mitochondrial tRNAs Bearing a Pathogenic A4317G or A10044G Mutation^*

Yukihide Tomari, Narumi Hino, Takashi Nagaike, Tsutomu Suzuki^§, and Takuya Ueda

From the Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba Prefecture 277-8562, Japan

Pathogenic point mutations in mitochondrial tRNA genes are known to cause a variety of human mitochondrial diseases. Reports have associated an A4317G mutation in the mitochondrial tRNA^Ile gene with fatal infantile cardiomyopathy and an A10044G mutation in the mitochondrial tRNA^Gly gene with sudden infant death syndrome. Here we demonstrate that both mutations inhibit in vitro CCA-addition to the respective tRNA by the human mitochondrial CCA-adding enzyme. Structures of these two mutant tRNAs were examined by nuclease probing. In the case of the A4317G tRNA^Ile mutant, structural rearrangement of the T-arm region, conferring an aberrantly stable T-arm structure and an increased T_m value, was clearly observed. In the case of the A10044G tRNA^Gly mutant, high nuclease sensitivity in both the T- and D-loops suggested a weakened interaction between the loops. These are the first reported instances of inefficient CCA-addition being one of the apparent molecular pathogeneses caused by pathogenic point mutations in human mitochondrial tRNA genes.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				L. Bonnefond, C. Florentz, R. Giege, and J. Rudinger-Thirion Decreased aminoacylation in pathology-related mutants of mitochondrial tRNATyr is associated with structural perturbations in tRNA architecture RNA, April 1, 2008; 14(4): 641 - 648. [Abstract] [Full Text] [PDF]

				J. Ling, H. Roy, D. Qin, M. A. T. Rubio, J. D. Alfonzo, K. Fredrick, and M. Ibba Pathogenic mechanism of a human mitochondrial tRNAPhe mutation associated with myoclonic epilepsy with ragged red fibers syndrome PNAS, September 25, 2007; 104(39): 15299 - 15304. [Abstract] [Full Text] [PDF]

				L. Levinger, M. Morl, and C. Florentz Mitochondrial tRNA 3' end metabolism and human disease Nucleic Acids Res., October 11, 2004; 32(18): 5430 - 5441. [Abstract] [Full Text] [PDF]

				N. Hino, T. Suzuki, T. Yasukawa, K. Seio, K. Watanabe, and T. Ueda The pathogenic A4269G mutation in human mitochondrial tRNAIle alters the T-stem structure and decreases the binding affinity for elongation factor Tu Genes Cells, March 1, 2004; 9(3): 243 - 252. [Abstract] [Full Text] [PDF]

				R. J. Temperley, S. H. Seneca, K. Tonska, E. Bartnik, L. A. Bindoff, R. N. Lightowlers, and Z. M.A. Chrzanowska-Lightowlers Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria Hum. Mol. Genet., September 15, 2003; 12(18): 2341 - 2348. [Abstract] [Full Text] [PDF]