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<script type="text/javascript" src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.boots.min.js"> </script><title>Cytosolic help for mitochondrial defects - Coffee Break - NCBI Bookshelf</title>
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title="Dismiss find">✘</a></nav><nav id="jr-fip-info-p"><a id="jr-fip-prev" class="wsprkl btn" title="Jump to previuos match">◀</a><button id="jr-fip-matches">no matches yet</button><a id="jr-fip-next" class="wsprkl btn" title="Jump to next match">▶</a></nav></nav></div><div id="jr-epub-interstitial" class="hidden"></div><div id="jr-content"><article data-type="main"><div class="main-content lit-style" itemscope="itemscope" itemtype="http://schema.org/CreativeWork"><div class="meta-content fm-sec"><div class="fm-sec"><h1 id="_NBK2327_"><span class="title" itemprop="name">Cytosolic help for mitochondrial defects</span></h1><div class="subtitle">a novel method for importing tRNA into mitochondria in order to suppress mutations</div><p class="fm-aai"><a href="#_NBK2327_pubdet_">Publication Details</a></p></div></div><div class="body-content whole_rhythm" itemprop="text"><p>The mitochondrion has cut back its genome substantially since taking up
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residence in cells as a symbiont 1.5 billion years ago, but it retains its
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personal transcription, translation and protein-assembling systems, including
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its tRNA genes. Even so, the mitochondrion is not fully self-sufficient — to varying extents yeast, plants and protozoan cells can borrow nuclear-encoded
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tRNA molecules to ease the task of translating transcripts of their mitochondrial genes. New data indicate that nuclear-encoded tRNAs can even be used to salvage errors in mitochondrial transcripts.</p><p>
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<a class="figpopup" href="/books/NBK2327/figure/A555/?report=objectonly" target="object" rid-figpopup="figA555" rid-ob="figobA555">Figure 1</a>
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</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figA555" co-legend-rid="figlgndA555"><a href="/books/NBK2327/figure/A555/?report=objectonly" target="object" title="Figure" class="img_link icnblk_img figpopup" rid-figpopup="figA555" rid-ob="figobA555"><img class="small-thumb" src="/books/NBK2327/bin/cb17a_big.gif" src-large="/books/NBK2327/bin/cb17a_big.jpg" alt="Tertiary structure of tRNA." /></a><div class="icnblk_cntnt" id="figlgndA555"><h4 id="A555"><a href="/books/NBK2327/figure/A555/?report=objectonly" target="object" rid-ob="figobA555">Figure</a></h4><p class="float-caption no_bottom_margin">Tertiary structure of tRNA. The anticodon loop and stem of tRNA<sup>Lys</sup> is depicted in the image to the left. The three bases that compose the anticodon (in this example, "U-U-U") are highlighted in yellow. </p></div></div><p>In the yeast <i>Saccharomyces cerevisiae,</i> only one tRNA (<sup>Lys</sup><sub>CUU</sub>) is carried into the mitochondrion, something it can do only if charged with an amino acid, and only if aided by cytosolic import factors. Among these factors is the precursor of the mitochondrial lysyl-tRNA synthetase (pre-MSK).</p><p>
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<a class="figpopup" href="/books/NBK2327/figure/A556/?report=objectonly" target="object" rid-figpopup="figA556" rid-ob="figobA556">Figure 2</a>
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</p><div class="iconblock whole_rhythm clearfix ten_col fig" id="figA556" co-legend-rid="figlgndA556"><a href="/books/NBK2327/figure/A556/?report=objectonly" target="object" title="Figure" class="img_link icnblk_img figpopup" rid-figpopup="figA556" rid-ob="figobA556"><img class="small-thumb" src="/books/NBK2327/bin/cb17b_big.gif" src-large="/books/NBK2327/bin/cb17b_big.jpg" alt="Mutation of the anticodon of tRNA." /></a><div class="icnblk_cntnt" id="figlgndA556"><h4 id="A556"><a href="/books/NBK2327/figure/A556/?report=objectonly" target="object" rid-ob="figobA556">Figure</a></h4><p class="float-caption no_bottom_margin">Mutation of the anticodon of tRNA. Outside of the mitochondria, tRNA<sup>Lys</sup>
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<sub>CUU</sub> is charged with lysine, its cognate amino acid. However, by changing the anticodon from C-U-U to C-A-U, the mutated tRNA is subsequently charged with methionine. To be able to <a href="/books/NBK2327/figure/A556/?report=objectonly" target="object" rid-ob="figobA556">(more...)</a></p></div></div><p>In a recent <a href="/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10988073&dopt=Abstract" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><u>publication</u></a>, researchers altered the aminoacylation identity of tRNA<sup>Lys</sup>
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<sub>CUU</sub> so that it was charged with methionine rather than lysine. Both in live yeast cells and in isolated mitochondria, the engineered tRNA could enter the mitochondrion, where the radiolabelled methionine charged on the imported tRNA was incorporated normally into mitochondrial proteins. A second, modified tRNA<sup>Lys</sup> version with alanine identity was also successfully used <i>in vivo</i> to suppress an <i>amber</i> (UAG) stop codon (a nonsense mutation) in the mitochondrial <i> COX2</i> gene.</p><p>Defects in mitochondrial (mt) DNA, caused by base substitutions or rearrangements in genes that encode proteins or tRNAs underlie a range of human pathologies (as discussed in the previous highlight).</p><p>Could the technique used to modify mitochondrial mutations be adapted for use in humans, given that import of nuclear-encoded tRNAs into mammalian mitochondria has never been seen? It seems so, because isolated human mitochondria imported the yeast tRNA<sup>Lys</sup>
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<sub>CUU</sub> and its derivatives, provided that the human cytosolic extracts were supplemented with the yeast pre-MSK. The foreign tRNA was functional on the translational apparatus of human mitochondria, just as in yeast.</p><p>This recent innovation might be useful for replacing non-functional tRNAs or for suppressing nonsense mutations in mtDNA.</p><p>Story contributed by Tanita Casci, <a href="http://www.nature.com/nrg/index.html" ref="pagearea=body&targetsite=external&targetcat=link&targettype=uri"><u>Nature Reviews Genetics</u></a>
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</p><p>
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</p><div id="A401" class="box boxed-text-box whole_rhythm hide-overflow"><h3><span class="title">Search Organelle Genome Resources</span></h3><p>Created: December 4, 2000</p><p>Click on the link below to start an html tutorial.</p><p>
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Evolution and the mitochondrial gene order of tRNAs</p></div><div id="bk_toc_contnr"></div></div></div><div class="fm-sec"><h2 id="_NBK2327_pubdet_">Publication Details</h2><h3>Publication History</h3><p class="small">Created: <span itemprop="datePublished">December 4, 2000</span>.</p><h3>Copyright</h3><div><div class="half_rhythm"><a href="/books/about/copyright/">Copyright Notice</a></div></div><h3>Publisher</h3><p><a href="http://www.ncbi.nlm.nih.gov/" ref="pagearea=page-banner&targetsite=external&targetcat=link&targettype=publisher">National Center for Biotechnology Information (US)</a>, Bethesda (MD)</p><h3>NLM Citation</h3><p>Dean L, McEntyre J, editors. Coffee Break: Tutorials for NCBI Tools [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 1999-. Cytosolic help for mitochondrial defects: a novel method for importing tRNA into mitochondria in order to suppress mutations. 2000 Dec 4.<span class="bk_cite_avail"></span></p></div><div class="small-screen-prev"><a href="/books/n/coffeebrk/A28/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M75,30 c-80,60 -80,0 0,60 c-30,-60 -30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Prev</text></svg></a></div><div class="small-screen-next"><a href="/books/n/coffeebrk/A26/?report=reader"><svg xmlns="http://www.w3.org/2000/svg" viewBox="0 0 100 100" preserveAspectRatio="none"><path d="M25,30c80,60 80,0 0,60 c30,-60 30,0 0,-60"></path><text x="20" y="28" textLength="60" style="font-size:25px">Next</text></svg></a></div></article><article data-type="fig" id="figobA555"><div id="A555" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK2327/bin/cb17a_big.jpg" alt="Tertiary structure of tRNA." /></div><h3><span class="title">Tertiary structure of tRNA</span></h3><div class="caption"><p><br />The anticodon loop and stem of tRNA<sup>Lys</sup> is depicted in the image to the left. The three bases that compose the anticodon (in this example, "U-U-U") are highlighted in yellow.</p></div></div></article><article data-type="fig" id="figobA556"><div id="A556" class="figure bk_fig"><div class="graphic"><img data-src="/books/NBK2327/bin/cb17b_big.jpg" alt="Mutation of the anticodon of tRNA." /></div><h3><span class="title">Mutation of the anticodon of tRNA</span></h3><div class="caption"><p><br />Outside of the mitochondria, tRNA<sup>Lys</sup>
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<sub>CUU</sub> is charged with lysine, its cognate amino acid. However, by changing the anticodon from C-U-U to C-A-U, the mutated tRNA is subsequently charged with methionine. To be able to track mutant tRNAs, an <sup>35</sup>S-radiolabelled methionine was used. This experiment demonstrated that aminoacylation was necessary for transport of tRNA into the mitochondria, although the identity of the amino acid that was charged onto the tRNA was less important.</p></div></div></article><article data-type="boxed-text" id="figobA401"><div id="A401" class="box boxed-text-box whole_rhythm hide-overflow"><h3><span class="title">Search Organelle Genome Resources</span></h3><p>Created: December 4, 2000</p><p>Click on the link below to start an html tutorial.</p><p>
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Evolution and the mitochondrial gene order of tRNAs</p></div></article></div><div id="jr-scripts"><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/libs.min.js"> </script><script src="/corehtml/pmc/jatsreader/ptpmc_3.22/js/jr.min.js"> </script></div></div>
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