TY  - JOUR
A1  - Valleriani, Angelo
A1  - Zhang, Gong
A1  - Nagar, Apoorva
A1  - Ignatova, Zoya
A1  - Lipowsky, Reinhard
T1  - Length-dependent translation of messenger RNA by ribosomes
JF  - Physical review : E, Statistical, nonlinear and soft matter physics
N2  - 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.
Y1  - 2011
U6  - https://doi.org/10.1103/PhysRevE.83.042903
SN  - 1539-3755
VL  - 83
IS  - 4
PB  - American Physical Society
CY  - College Park
ER  - 
TY  - JOUR
A1  - Borwankar, Tejas
A1  - Roethlein, Christoph
A1  - Zhang, Gong
A1  - Techen, Anne
A1  - Dosche, Carsten
A1  - Ignatova, Zoya
T1  - Natural osmolytes remodel the aggregation pathway of mutant huntingtin exon 1
JF  - Biochemistry
N2  - 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.
Y1  - 2011
U6  - https://doi.org/10.1021/bi1018368
SN  - 0006-2960
VL  - 50
IS  - 12
SP  - 2048
EP  - 2060
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Zhang, Gong
A1  - Lukoszek, Radoslaw
A1  - Müller-Röber, Bernd
A1  - Ignatova, Zoya
T1  - Different sequence signatures in the upstream regions of plant and animal tRNA genes shape distinct modes of regulation
JF  - Nucleic acids research
N2  - 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.
Y1  - 2011
U6  - https://doi.org/10.1093/nar/gkq1257
SN  - 0305-1048
VL  - 39
IS  - 8
SP  - 3331
EP  - 3339
PB  - Oxford Univ. Press
CY  - Oxford
ER  -