TY  - GEN
A1  - Gorochowski, Thomas E.
A1  - Ignatova, Zoya
A1  - Bovenberg, Roel A. L.
A1  - Roubos, Johannes A.
T1  - Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Translation of protein from mRNA is a complex multi-step process that occurs at a non-uniform rate. Variability in ribosome speed along an mRNA enables refinement of the proteome and plays a critical role in protein biogenesis. Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency. Here we provide evidence that this results from an inherent trade-off between these factors. We find codons pairing to high-abundance tRNAs are preferentially used in regions of high secondary structure content, while codons read by significantly less abundant tRNAs are located in lowly structured regions. By considering long stretches of high and low mRNA secondary structure in Saccharomyces cerevisiae and Escherichia coli and comparing them to randomized-gene models and experimental expression data, we were able to distinguish clear selective pressures and increased protein expression for specific codon choices. The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 816 
KW  - Escherichia-coli genome
KW  - codon adaptation index
KW  - folding free-energies
KW  - in-vivo
KW  - sequence determinants
KW  - protein-synthesis
KW  - single ribosomes
KW  - gene-expression
KW  - usage
KW  - bias
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-441340
SN  - 1866-8372
IS  - 816
ER  - 
TY  - GEN
A1  - Del Campo, Cristian
A1  - Bartholomäus, Alexander
A1  - Fedyunin, Ivan
A1  - Ignatova, Zoya
T1  - Secondary Structure across the Bacterial Transcriptome Reveals Versatile Roles in mRNA Regulation and Function
T2  - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe
N2  - Messenger RNA acts as an informational molecule between DNA and translating ribosomes. Emerging evidence places mRNA in central cellular processes beyond its major function as informational entity. Although individual examples show that specific structural features of mRNA regulate translation and transcript stability, their role and function throughout the bacterial transcriptome remains unknown. Combining three sequencing approaches to provide a high resolution view of global mRNA secondary structure, translation efficiency and mRNA abundance, we unraveled structural features in E. coli mRNA with implications in translation and mRNA degradation. A poorly structured site upstream of the coding sequence serves as an additional unspecific binding site of the ribosomes and the degree of its secondary structure propensity negatively correlates with gene expression. Secondary structures within coding sequences are highly dynamic and influence translation only within a very small subset of positions. A secondary structure upstream of the stop codon is enriched in genes terminated by UAA codon with likely implications in translation termination. The global analysis further substantiates a common recognition signature of RNase E to initiate endonucleolytic cleavage. This work determines for the first time the E. coli RNA structurome, highlighting the contribution of mRNA secondary structure as a direct effector of a variety of processes, including translation and mRNA degradation.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 520 
KW  - Escherichia coli
KW  - in vivo
KW  - translation initiation
KW  - crystal-structure
KW  - single ribosomes
KW  - gene-expression
KW  - global analysis
KW  - codon usage
KW  - E-cleavage
KW  - genome
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-409662
SN  - 1866-8372
IS  - 520
ER  -