@article{VallerianiZhangNagaretal.2011, author = {Valleriani, Angelo and Zhang, Gong and Nagar, Apoorva and Ignatova, Zoya and Lipowsky, Reinhard}, title = {Length-dependent translation of messenger RNA by ribosomes}, series = {Physical review : E, Statistical, nonlinear and soft matter physics}, volume = {83}, journal = {Physical review : E, Statistical, nonlinear and soft matter physics}, number = {4}, publisher = {American Physical Society}, address = {College Park}, issn = {1539-3755}, doi = {10.1103/PhysRevE.83.042903}, pages = {4}, year = {2011}, abstract = {A simple measure for the efficiency of protein synthesis by ribosomes is provided by the steady state amount of protein per messenger RNA (mRNA), the so-called translational ratio, which is proportional to the translation rate. Taking the degradation of mRNA into account, we show theoretically that both the translation rate and the translational ratio decrease with increasing mRNA length, in agreement with available experimental data for the prokaryote Escherichia coli. We also show that, compared to prokaryotes, mRNA degradation in eukaryotes leads to a less rapid decrease of the translational ratio. This finding is consistent with the fact that, compared to prokaryotes, eukaryotes tend to have longer proteins.}, language = {en} } @article{BorwankarRoethleinZhangetal.2011, author = {Borwankar, Tejas and Roethlein, Christoph and Zhang, Gong and Techen, Anne and Dosche, Carsten and Ignatova, Zoya}, title = {Natural osmolytes remodel the aggregation pathway of mutant huntingtin exon 1}, series = {Biochemistry}, volume = {50}, journal = {Biochemistry}, number = {12}, publisher = {American Chemical Society}, address = {Washington}, issn = {0006-2960}, doi = {10.1021/bi1018368}, pages = {2048 -- 2060}, year = {2011}, abstract = {In response to stress small organic compounds termed osmolytes are ubiquitously accumulated in all cell types to regulate the intracellular solvent quality and to counteract the deleterious effect on the stability and function of cellular proteins. Given the evidence that destabilization of the native state of a protein either by mutation or by environmental changes triggers the aggregation in the neurodegenerative pathologies, the modulation of the intracellular solute composition with osmolytes is an attractive strategy to stabilize an aggregating protein. Here we report the effect of three natural osmolytes on the in vivo and in vitro aggregation landscape of huntingtin exon 1 implicated in the Huntington's disease. Trimethylamine N-oxide (TMAO) and proline redirect amyloid fibrillogenesis of the pathological huntingtin exon 1 to nonamyloidogenic amorphous assemblies via two dissimilar molecular mechanisms. TMAO causes a rapid formation of bulky amorphous aggregates with minimally exposed surface area, whereas proline solubilizes the monomer and suppresses the accumulation of early transient aggregates. Conversely, glycine betaine enhances fibrillization in a fashion reminiscent of the genesis of functional amyloids. Strikingly, none of the natural osmolytes can completely abrogate the aggregate formation; however, they redirect the amyloidogenesis into alternative, nontoxic aggregate species. Our study reveals new insights into the complex interactions of osmoprotectants with polyQaggregates.}, language = {en} } @misc{ZhangIgnatova2011, author = {Zhang, Gong and Ignatova, Zoya}, title = {Folding at the birth of the nascent chain: coordinating translation with co-translational folding}, series = {Current opinion in structural biology : review of all advances ; evaluation of key references ; comprehensive listing of papers}, volume = {21}, journal = {Current opinion in structural biology : review of all advances ; evaluation of key references ; comprehensive listing of papers}, number = {1}, publisher = {Elsevier}, address = {London}, issn = {0959-440X}, doi = {10.1016/j.sbi.2010.10.008}, pages = {25 -- 31}, year = {2011}, abstract = {In the living cells, the folding of many proteins is largely believed to begin co-translationally, during their biosynthesis at the ribosomes. In the ribosomal tunnel, the nascent peptide may establish local interactions and stabilize alpha-helical structures. Long-range contacts are more likely outside the ribosomes after release of larger segments of the nascent chain. Examples suggest that domains can attain native-like structure on the ribosome with and without population of folding intermediates. The co-translational folding is limited by the speed of the gradual extrusion of the nascent peptide which imposes conformational restraints on its folding landscape. Recent experimental and in silico modeling studies indicate that translation kinetics fine-tunes co-translational folding by providing a time delay for sequential folding of distinct portions of the nascent chain.}, language = {en} } @article{ZhangLukoszekMuellerRoeberetal.2011, author = {Zhang, Gong and Lukoszek, Radoslaw and M{\"u}ller-R{\"o}ber, Bernd and Ignatova, Zoya}, title = {Different sequence signatures in the upstream regions of plant and animal tRNA genes shape distinct modes of regulation}, series = {Nucleic acids research}, volume = {39}, journal = {Nucleic acids research}, number = {8}, publisher = {Oxford Univ. Press}, address = {Oxford}, issn = {0305-1048}, doi = {10.1093/nar/gkq1257}, pages = {3331 -- 3339}, year = {2011}, abstract = {In eukaryotes, the transcription of tRNA genes is initiated by the concerted action of transcription factors IIIC (TFIIIC) and IIIB (TFIIIB) which direct the recruitment of polymerase III. While TFIIIC recognizes highly conserved, intragenic promoter elements, TFIIIB binds to the non-coding 5'-upstream regions of the tRNA genes. Using a systematic bioinformatic analysis of 11 multicellular eukaryotic genomes we identified a highly conserved TATA motif followed by a CAA-motif in the tRNA upstream regions of all plant genomes. Strikingly, the 5'-flanking tRNA regions of the animal genomes are highly heterogeneous and lack a common conserved sequence signature. Interestingly, in the animal genomes the tRNA species that read the same codon share conserved motifs in their upstream regions. Deep-sequencing analysis of 16 human tissues revealed multiple splicing variants of two of the TFIIIB subunits, Bdp1 and Brf1, with tissue-specific expression patterns. These multiple forms most likely modulate the TFIIIB-DNA interactions and explain the lack of a uniform signature motif in the tRNA upstream regions of animal genomes. The anticodon-dependent 5'-flanking motifs provide a possible mechanism for independent regulation of the tRNA transcription in various human tissues.}, language = {en} }