@article{BenteleSaffertRauscheretal.2013, author = {Bentele, Kajetan and Saffert, Paul and Rauscher, Robert and Ignatova, Zoya and Bluethgen, Nils}, title = {Efficient translation initiation dictates codon usage at gene start}, series = {Molecular systems biology}, volume = {9}, journal = {Molecular systems biology}, number = {6}, publisher = {Nature Publ. Group}, address = {New York}, issn = {1744-4292}, doi = {10.1038/msb.2013.32}, pages = {10}, year = {2013}, abstract = {The genetic code is degenerate; thus, protein evolution does not uniquely determine the coding sequence. One of the puzzles in evolutionary genetics is therefore to uncover evolutionary driving forces that result in specific codon choice. In many bacteria, the first 5-10 codons of protein-coding genes are often codons that are less frequently used in the rest of the genome, an effect that has been argued to arise from selection for slowed early elongation to reduce ribosome traffic jams. However, genome analysis across many species has demonstrated that the region shows reduced mRNA folding consistent with pressure for efficient translation initiation. This raises the possibility that unusual codon usage is a side effect of selection for reduced mRNA structure. Here we discriminate between these two competing hypotheses, and show that in bacteria selection favours codons that reduce mRNA folding around the translation start, regardless of whether these codons are frequent or rare. Experiments confirm that primarily mRNA structure, and not codon usage, at the beginning of genes determines the translation rate.}, language = {en} } @article{CzechWendeMoerletal.2013, author = {Czech, Andreas and Wende, Sandra and Moerl, Mario and Pan, Tao and Ignatova, Zoya}, title = {Reversible and rapid transfer-RNA deactivation as a mechanism of translational repression in stress}, series = {PLoS Genetics : a peer-reviewed, open-access journal}, volume = {9}, journal = {PLoS Genetics : a peer-reviewed, open-access journal}, number = {8}, publisher = {PLoS}, address = {San Fransisco}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003767}, pages = {9}, year = {2013}, abstract = {Stress-induced changes of gene expression are crucial for survival of eukaryotic cells. Regulation at the level of translation provides the necessary plasticity for immediate changes of cellular activities and protein levels. In this study, we demonstrate that exposure to oxidative stress results in a quick repression of translation by deactivation of the aminoacylends of all transfer-RNA (tRNA). An oxidative-stress activated nuclease, angiogenin, cleaves first within the conserved single-stranded 3'-CCA termini of all tRNAs, thereby blocking their use in translation. This CCA deactivation is reversible and quickly repairable by the CCA-adding enzyme [ATP(CTP): tRNA nucleotidyltransferase]. Through this mechanism the eukaryotic cell dynamically represses and reactivates translation at low metabolic costs.}, language = {en} } @article{GirstmairSaffertRodeetal.2013, author = {Girstmair, Hannah and Saffert, Paul and Rode, Sascha and Czech, Andreas and Holland, Gudrun and Bannert, Norbert and Ignatova, Zoya}, title = {Depletion of Cognate Charged Transfer RNA Causes Translational Frameshifting within the Expanded CAG Stretch in Huntingtin}, series = {Cell reports}, volume = {3}, journal = {Cell reports}, number = {1}, publisher = {Cell Press}, address = {Cambridge}, issn = {2211-1247}, doi = {10.1016/j.celrep.2012.12.019}, pages = {148 -- 159}, year = {2013}, abstract = {Huntington disease (HD), a dominantly inherited neurodegenerative disorder caused by the expansion of a CAG-encoded polyglutamine (polyQ) repeat in huntingtin (Htt), displays a highly heterogeneous etiopathology and disease onset. Here, we show that the translation of expanded CAG repeats in mutant Htt exon 1 leads to a depletion of charged glutaminyl-transfer RNA (tRNA) Gln-CUG that pairs exclusively to the CAG codon. This results in translational frameshifting and the generation of various transframe-encoded species that differently modulate the conformational switch to nucleate fibrillization of the parental polyQ protein. Intriguingly, the frameshifting frequency varies strongly among different cell lines and is higher in cells with intrinsically lower concentrations of tRNA Gln-CUG. The concentration of tRNA Gln-CUG also differs among different brain areas in the mouse. We propose that translational frameshifting may act as a significant disease modifier that contributes to the cell-selective neurotoxicity and disease course heterogeneity of HD on both cellular and individual levels.}, language = {en} } @article{LukoszekMuellerRoeberIgnatova2013, author = {Lukoszek, Radoslaw and M{\"u}ller-R{\"o}ber, Bernd and Ignatova, Zoya}, title = {Interplay between polymerase II- and polymerase III-assisted expression of overlapping genes}, series = {FEBS letters : the journal for rapid publication of short reports in molecular biosciences}, volume = {587}, journal = {FEBS letters : the journal for rapid publication of short reports in molecular biosciences}, number = {22}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0014-5793}, doi = {10.1016/j.febslet.2013.09.033}, pages = {3692 -- 3695}, year = {2013}, abstract = {Up to 15\% of the genes in different genomes overlap. This architecture, although beneficial for the genome size, represents an obstacle for simultaneous transcription of both genes. Here we analyze the interference between RNA-polymerase II (Pol II) and RNA-polymerase III (Pol III) when transcribing their target genes encoded on opposing strands within the same DNA fragment in Arabidopsis thaliana. The expression of a Pol II-dependent protein-coding gene negatively correlated with the transcription of a Pol III-dependent, tRNA-coding gene set. We suggest that the architecture of the overlapping genes introduces an additional layer of control of gene expression. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.}, language = {en} }