Human mitochondrial leucyl tRNA synthetase can suppress non cognate pathogenic mt‐tRNA mutations. Issue 2 (10th January 2014)

• Record Type: Journal Article
• Authors: Hornig‐Do, Hue Tran; Montanari, Arianna; Rozanska, Agata; Tuppen, Helen A; Almalki, Abdulraheem A; Abg‐Kamaludin, Dyg P; Frontali, Laura; Francisci, Silvia; Lightowlers, Robert N; Chrzanowska‐Lightowlers, Zofia M
• Is Part Of: EMBO molecular medicine. Volume 6:Issue 2(2014:Feb.)
• Page Start: 183
• Page End: 193
• Publication Date: 2014-01-10
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201303202
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="synopsis" xml:lang="en" id="emmm201303202-abs-0002"> <title>Synopsis</title> <p> <boxed-text content-type="graphic" id="emmm201303202-blkfxd-0001" position="anchor" orientation="portrait"> <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg4snhp01w" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </boxed-text> </p> <p>A non‐cognate mitochondrial aminoacyl tRNA synthetase can overcome the respiratory defect caused by an mt‐tRNA mutation. The pathogenic mutation can be suppressed by a short peptide corresponding to the C‐terminus of leucyl tRNA synthetase.</p> <p> <list id="emmm201303202-list-0004" list-type="bullet"> <list-item> <p>Human mitochondrial leucyl tRNA synthetase (LARS2) can bind many species of mt‐tRNAs, not exclusively mt‐tRNAleu(UUR) or mt‐tRNAleu(CUN)</p> </list-item> <list-item> <p>Binding can stabilize mt‐tRNAs that carry pathogenic destabilizing mutations such as that generated from the m.1624C&gt;T in the gene encoding mt‐tRNAVal</p> </list-item> <list-item> <p>A C‐terminal peptide of LARS2 is able to access the mitochondrial matrix and bind a similar spectrum of mt‐tRNAs to the complete LARS2 protein</p> </list-item> <list-item> <p>This short peptide has potential to be a therapeutic molecule for many pathogenic mt‐tRNA mutations.</p> </list-item> </list> </p> </abstract>