A tRNA suppressor mutation in human mitochondria

Nature Genetics
A El MezianeHoward T Jacobs

Abstract

Mitochondrial mutations are associated with a wide spectrum of human diseases. A common class of point mutations affects tRNA genes, and mutations in the tRNA-leu(UUR) gene (MTTL1) are the most frequently detected. In earlier studies, we showed that lung carcinoma cybrid cells containing high levels (greater than 95%) of mutated mtDNA from a patient with the pathological nucleotide pair (np) 3243 tRNA-leu(UUR) mutation can remain genotypically stable over time, and exhibit severe defects in mitochondrial respiratory metabolism. From such a cybrid containing 99% mutated mtDNA, we have isolated a spontaneous derivative that retains mutant mtDNA at this level but which has nevertheless reverted to the wild-type phenotype, based on studies of respiration, growth in selective media, mitochondrial protein synthesis and biogenesis of mitochondrial membrane complexes. The cells are heteroplasmic for a novel anticodon mutation in tRNA-leu(CUN) at np 12300, predicted to generate a suppressor tRNA capable of decoding UUR leucine codons. The suppressor mutation represents approximately 10% of the total mtDNA, but was undetectable in a muscle biopsy sample taken from the original patient or in the parental cybrid. These results indicate tha...Continue Reading

References

Feb 25, 1991·Nucleic Acids Research·D PagesR H Buckingham
Jun 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·J E HeckmanU L RajBhandary
Apr 9, 1981·Nature·S AndersonI G Young
Jul 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·D R DunbarI J Holt
Jul 1, 1993·Nature Genetics·C T MoraesS DiMauro
Dec 12, 1995·Biochimica Et Biophysica Acta·L G NijtmansC van den Bogert
Aug 1, 1996·Annals of Neurology·P KaufmannE A Schon
Jan 1, 1995·Annual Review of Genetics·N G Larsson, D A Clayton
Mar 1, 1996·Seminars in Neurology·R Fadic, D R Johns

❮ Previous
Next ❯

Citations

Apr 23, 2013·Biochemical Genetics·Yu DingPan Xu
May 6, 2003·Journal of Molecular Biology·Bénédicte SohmCatherine Florentz
May 30, 2001·Advanced Drug Delivery Reviews·T Pulkes, M G Hanna
Nov 14, 2000·Molecular Medicine Today·P F Chinnery, D M Turnbull
May 17, 2002·Nihon rinsho. Japanese journal of clinical medicine·Takehiro YasukawaShigeo Ohta
Aug 27, 2005·Mitochondrion·M Pilar Bayona-BafaluyJosé A Enríquez
Aug 27, 2005·Mitochondrion·Anna LorencEwa Bartnik
Apr 30, 2005·Nature Reviews. Genetics·Robert W Taylor, Doug M Turnbull
Sep 8, 2005·Rejuvenation Research·Rafal M Smigrodzki, Shaharyar M Khan
Aug 21, 2003·Human Molecular Genetics·Howard T Jacobs
Mar 14, 2008·Human Molecular Genetics·Sabrina SacconiMercy M Davidson
Jun 30, 2009·Human Molecular Genetics·Adriana MalenaLodovica Vergani
Dec 7, 2000·Evolution; International Journal of Organic Evolution·A Poon, S P Otto
Jan 24, 2006·Molecular and Cellular Biology·Jian-Hong DengYidong Bai
Dec 6, 2000·Microbiology and Molecular Biology Reviews : MMBR·C G Kurland, S G Andersson
Dec 16, 2003·Proceedings of the National Academy of Sciences of the United States of America·Timothy A RawlingsRudiger Bieler
Apr 28, 2012·Mitochondrion·Jing ZhengMin-Xin Guan
May 6, 2008·Experimental Neurology·Jacopo C DiFrancescoAntony H Schapira
Oct 1, 2011·Wiley Interdisciplinary Reviews. RNA·Tsutomu SuzukiTakeo Suzuki
Feb 19, 2015·RNA Biology·L Peter Sarin, Sebastian A Leidel
Aug 1, 2015·Nucleic Acids Research·Abdullah H SahyounMatthias Bernt
Sep 19, 2012·Molecular and Cellular Neurosciences·Sarah PearceAntonella Spinazzola
Oct 9, 2008·Biochimica Et Biophysica Acta·Julio MontoyaEduardo Ruiz-Pesini
Sep 19, 2009·Biochimica Et Biophysica Acta·Helen A L TuppenRobert W Taylor
Feb 7, 2008·American Journal of Human Genetics·Harsha Karur RajasimhaDavid C Samuels
Dec 29, 1998·American Journal of Human Genetics·N Howell, D A Mackey
Aug 5, 2004·European Journal of Human Genetics : EJHG·Howard T JacobsRobert F Mueller
Jul 10, 2018·International Journal of Geriatric Psychiatry·Gregory J TranahUNKNOWN Health, Aging and Body Composition Study

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.