Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (426K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (38)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Li, X.
Right arrow Articles by Guan, M.-X.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, X.
Right arrow Articles by Guan, M.-X.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Published online 11 February 2004

Nucleic Acids Research, 2004, Vol. 32, No. 3 867-877
© 2004 Oxford University Press

Biochemical characterization of the mitochondrial tRNASer(UCN) T7511C mutation associated with nonsyndromic deafness

Xiaoming Li1, Nathan Fischel-Ghodsian2, Faina Schwartz3, Qingfeng Yan1, Rick A. Friedman4 and Min-Xin Guan*,1,5

1 Division and Program in Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA, 2 Ahmanson Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA, 3 Boston University School of Medicine, Boston, MA 02118, USA, 4 House Ear Clinic and House Ear Institute, Los Angeles, CA 90057, USA and 5 Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA

*To whom correspondence should be addressed. Tel: +1 513 636 3337; Fax: +1 513 636 3486; Email: min-xin.guan{at}chmcc.org

We report here the biochemical characterization of the deafness-associated mitochondrial tRNASer(UCN) T7511C mutation, in conjunction with homoplasmic ND1 T3308C and tRNAAla T5655C mutations using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from an African family into human mtDNA-less ({rho}°) cells. Three cybrids derived from an affected matrilineal relative carrying the homoplasmic T7511C mutation, exhibited ~75% decrease in the tRNASer(UCN) level, compared with three control cybrids. This amount of reduction in the tRNASer(UCN) level is below a proposed threshold to support a normal rate of mitochondrial protein synthesis in lymphoblastoid cell lines. This defect is likely a primary contributor to ~52% reduction in the rate of mitochondrial protein synthesis and marked defects in respiration and growth properties in galactose-containing medium. Interestingly, the T5655C mutation produces ~50% reduction in the tRNAAla level in mutant cells. Strikingly, the T3308C mutation causes a significant decrease both in the amount of ND1 mRNA and co-transcribed tRNALeu(UUR) in mutant cells. Thus, mitochondrial dysfunctions caused by the T5655C and T3308C mutations may modulate the phenotypic manifestation of the T7511C mutation. These observations imply that a combination of the T7511C mutation with two mtDNA mutations accounts for the high penetrance of deafness in this family.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 HypertensionHome page
R. Li, Y. Liu, Z. Li, L. Yang, S. Wang, and M.-X. Guan
Failures in Mitochondrial tRNAMet and tRNAGln Metabolism Caused by the Novel 4401A>G Mutation Are Involved in Essential Hypertension in a Han Chinese Family
Hypertension, August 1, 2009; 54(2): 329 - 337.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
Y. Liu, R. Li, Z. Li, X.-J. Wang, L. Yang, S. Wang, and M.-X. Guan
Mitochondrial Transfer RNAMet 4435A>G Mutation Is Associated With Maternally Inherited Hypertension in a Chinese Pedigree
Hypertension, June 1, 2009; 53(6): 1083 - 1090.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
M. F. Mehler and J. S. Mattick
Noncoding RNAs and RNA Editing in Brain Development, Functional Diversification, and Neurological Disease
Physiol Rev, July 1, 2007; 87(3): 799 - 823.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
J. Qu, R. Li, X. Zhou, Y. Tong, F. Lu, Y. Qian, Y. Hu, J. Q. Mo, C. E. West, and M.-X. Guan
The Novel A4435G Mutation in the Mitochondrial tRNAMet May Modulate the Phenotypic Expression of the LHON-Associated ND4 G11778A Mutation
Invest. Ophthalmol. Vis. Sci., February 1, 2006; 47(2): 475 - 483.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
H. Zhao, W.-Y. Young, Q. Yan, R. Li, J. Cao, Q. Wang, X. Li, J. L. Peters, D. Han, and M.-X. Guan
Functional characterization of the mitochondrial 12S rRNA C1494T mutation associated with aminoglycoside-induced and non-syndromic hearing loss
Nucleic Acids Res., February 18, 2005; 33(3): 1132 - 1139.
[Abstract] [Full Text] [PDF]

Home page
 J. Med. Genet.Home page
R Li, J H Greinwald Jr, L Yang, D I Choo, R J Wenstrup, and M-X Guan
Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss
J. Med. Genet., August 1, 2004; 41(8): 615 - 620.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.