The presence of highly disruptive 16S rRNA mutations in clinical samples indicates a wider role for mutations of the mitochondrial ribosome in human disease

Mitochondrion
Joanna L ElsonAntón Vila-Sanjurjo

Abstract

Mitochondrial DNA mutations are well recognized as an important cause of disease, with over two hundred variants in the protein encoding and mt-tRNA genes associated with human disorders. In contrast, the two genes encoding the mitochondrial rRNAs (mt-rRNAs) have been studied in far less detail. This is because establishing the pathogenicity of mt-rRNA mutations is a major diagnostic challenge. Only two disease causing mutations have been identified at these loci, both mapping to the small subunit (SSU). On the large subunit (LSU), however, the evidence for the presence of pathogenic LSU mt-rRNA changes is particularly sparse. We have previously expanded the list of deleterious SSU mt-rRNA mutations by identifying highly disruptive base changes capable of blocking the activity of the mitoribosomal SSU. To do this, we used a new methodology named heterologous inferential analysis (HIA). The recent arrival of near-atomic-resolution structures of the human mitoribosomal LSU, has enhanced the power of our approach by permitting the analysis of the corresponding sites of mutation within their natural structural context. Here, we have used these tools to determine whether LSU mt-rRNA mutations found in the context of human disease an...Continue Reading

References

Nov 1, 1968·Proceedings of the National Academy of Sciences of the United States of America·R E MonroK A Marcker
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·C Aagaard, S Douthwaite
Oct 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·M O'Connor, A E Dahlberg
Dec 1, 1995·Antimicrobial Agents and Chemotherapy·T S LucierP C Hu
Apr 14, 1999·Proceedings of the National Academy of Sciences of the United States of America·H C AuI E Scheffler
Feb 17, 2001·American Journal of Human Genetics·J L ElsonP F Chinnery
Apr 3, 2001·Science·M M YusupovH F Noller
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·J ThompsonA E Dahlberg
Mar 15, 2002·Cell·Hitoshi Nakatogawa, Koreaki Ito
Jul 24, 2002·Nucleic Acids Research·Kazutaka KatohTakashi Miyata
Nov 5, 2003·The Journal of Clinical Investigation·Robert W TaylorDouglass M Turnbull
Apr 22, 2004·Journal of Molecular Biology·François BélangerLéa Brakier-Gingras
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Oct 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yohei KirinoTsutomu Suzuki
Oct 27, 2004·Annals of Neurology·Chaya MillerOrly Elpeleg
Feb 8, 2005·Biochemical and Biophysical Research Communications·Jianhua XuM Clelia Ganoza
Aug 27, 2005·Mitochondrion·Anna LorencEwa Bartnik
Apr 4, 2006·Nature Chemical Biology·Oliver RackhamJason W Chin
Aug 8, 2006·The Journal of Biological Chemistry·Aivar Liiv, Michael O'Connor
Sep 9, 2006·Science·Maria SelmerV Ramakrishnan
Sep 16, 2006·Molecular Cell·Iraj K AliHarry F Noller
Dec 21, 2006·Nucleic Acids Research·Eduardo Ruiz-PesiniDouglas C Wallace
Apr 26, 2007·Proceedings of the National Academy of Sciences of the United States of America·Shaoyu ZhouJoseph A Califano
Aug 3, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Suhail K MithaniJoseph A Califano
Feb 1, 2008·PLoS Biology·James Bruce StewartNils-Göran Larsson
Apr 29, 2008·Molecular Cell·Nora Vazquez-LaslopAlexander S Mankin
Sep 17, 2008·International Journal of Cancer. Journal International Du Cancer·Sailesh GochhaitRameshwar N K Bamezai
Apr 14, 2009·Nature Structural & Molecular Biology·Rebecca M VoorheesV Ramakrishnan
Sep 1, 2009·Human Mutation·Joanna L ElsonDoug M Turnbull
Jan 26, 2010·Experimental Gerontology·Laura C GreavesDoug M Turnbull
Jun 15, 2010·Environmental and Molecular Mutagenesis·Douglas C Wallace
Dec 2, 2010·Molecular Biology of the Cell·Mateusz KolanczykStefan Mundlos
Dec 7, 2010·American Journal of Human Genetics·Anita Kloss-BrandstätterFlorian Kronenberg

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Citations

Oct 8, 2016·Autophagy·Lisa B FrankelAnders H Lund
Jun 18, 2017·Journal of Insect Physiology·Samuel G Towarnicki, J William O Ballard
Mar 10, 2018·Mitochondrial DNA. Part A. DNA Mapping, Sequencing, and Analysis·Qi-Lin ZhangMing-Long Yuan
Feb 27, 2020·Antioxidants & Redox Signaling·Ana Mafalda GonçalvesNuno Empadinhas
Oct 18, 2020·International Journal of Molecular Sciences·Michael Webb, Dionisia P Sideris
Nov 17, 2020·Autoimmunity·Kumar Sagar JaiswalBhawna Gupta
Dec 15, 2020·FEBS Letters·Alberto FerrariAntoni Barrientos
May 1, 2021·International Journal of Molecular Sciences·Maria Isabel G Lopez SanchezJoanna Rorbach
May 28, 2021·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Celine BrisVincent Procaccio

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Software Mentioned

PERL scripts
Entrez Programming Utilities
MITOMAP
CbeamM
MAFFT
PERL script
UCSF Chimera
Chimera

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