@article{GorochowskiAycilarKucukgozeBovenbergetal.2016,
  author    = {Gorochowski, Thomas E. and Aycilar-Kucukgoze, Irem and Bovenberg, Roel A. L. and Roubos, Johannes A. and Ignatova, Zoya},
  title     = {A Minimal Model of Ribosome Allocation Dynamics Captures Trade-offs in Expression between Endogenous and Synthetic Genes},
  series = {ACS synthetic biology},
  volume    = {5},
  journal   = {ACS synthetic biology},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {2161-5063},
  doi       = {10.1021/acssynbio.6b00040},
  pages     = {710 -- 720},
  year      = {2016},
  abstract  = {Cells contain a finite set of resources that must be distributed across many processes to ensure survival. Among them, the largest proportion of cellular resources is dedicated to protein translation. Synthetic biology often exploits these resources in executing orthogonal genetic circuits, yet the burden this places on the cell is rarely considered. Here, we develop a minimal model of ribosome allocation dynamics capturing the demands on translation when expressing a synthetic construct together with endogenous genes required for the maintenance of cell physiology. Critically, it contains three key variables related to design parameters of the synthetic construct covering transcript abundance, translation initiation rate, and elongation time. We show that model-predicted changes in ribosome allocation closely match experimental shifts in synthetic protein expression rate and cellular growth. Intriguingly, the model is also able to accurately infer transcript levels and translation times after further exposure to additional ambient stress. Our results demonstrate that a simple model of resource allocation faithfully captures the redistribution of protein synthesis resources when faced with the burden of synthetic gene expression and environmental stress. The tractable nature of the model makes it a versatile tool for exploring the guiding principles of efficient heterologous expression and the indirect interactions that can arise between synthetic circuits and their host chassis because of competition for shared translational resources.},
  language  = {en}
}
@article{SaffertAdamlaSchiewecketal.2016,
  author    = {Saffert, Paul and Adamla, Frauke and Schieweck, Rico and Atkins, John F. and Ignatova, Zoya},
  title     = {An Expanded CAG Repeat in Huntingtin Causes+1 Frameshifting},
  series = {The journal of biological chemistry},
  volume    = {291},
  journal   = {The journal of biological chemistry},
  publisher = {American Society for Biochemistry and Molecular Biology},
  address   = {Bethesda},
  issn      = {0021-9258},
  doi       = {10.1074/jbc.M116.744326},
  pages     = {18505 -- 18513},
  year      = {2016},
  abstract  = {Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5 end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1.},
  language  = {en}
}
@article{BartholomaeusFedyuninFeistetal.2016,
  author    = {Bartholom{\"a}us, Alexander and Fedyunin, Ivan and Feist, Peter and Sin, Celine and Zhang, Gong and Valleriani, Angelo and Ignatova, Zoya},
  title     = {Bacteria differently regulate mRNA abundance to specifically respond to various stresses},
  series = {Geology},
  volume    = {374},
  journal   = {Geology},
  publisher = {Royal Society},
  address   = {London},
  issn      = {1364-503X},
  doi       = {10.1098/rsta.2015.0069},
  pages     = {16},
  year      = {2016},
  abstract  = {Environmental stress is detrimental to cell viability and requires an adequate reprogramming of cellular activities to maximize cell survival. We present a global analysis of the response of Escherichia coli to acute heat and osmotic stress. We combine deep sequencing of total mRNA and ribosome-protected fragments to provide a genome-wide map of the stress response at transcriptional and translational levels. For each type of stress, we observe a unique subset of genes that shape the stress-specific response. Upon temperature upshift, mRNAs with reduced folding stability up-and downstream of the start codon, and thus with more accessible initiation regions, are translationally favoured. Conversely, osmotic upshift causes a global reduction of highly translated transcripts with high copy numbers, allowing reallocation of translation resources to not degraded and newly synthesized mRNAs.},
  language  = {en}
}
@article{AvcilarKucukgozeBartholomaeusVarelaetal.2016,
  author    = {Avcilar-Kucukgoze, Irem and Bartholom{\"a}us, Alexander and Varela, Juan A. Cordero and Kaml, Robert Franz-Xaver and Neubauer, Peter and Budisa, Nediljko and Ignatova, Zoya},
  title     = {Discharging tRNAs: a tug of war between translation and detoxification in Escherichia coli},
  series = {Nucleic acids research},
  volume    = {44},
  journal   = {Nucleic acids research},
  publisher = {Oxford Univ. Press},
  address   = {Oxford},
  issn      = {0305-1048},
  doi       = {10.1093/nar/gkw697},
  pages     = {8324 -- 8334},
  year      = {2016},
  abstract  = {Translation is a central cellular process and is optimized for speed and fidelity. The speed of translation of a single codon depends on the concentration of aminoacyl-tRNAs. Here, we used microarray-based approaches to analyze the charging levels of tRNAs in Escherichia coli growing at different growth rates. Strikingly, we observed a non-uniform aminoacylation of tRNAs in complex media. In contrast, in minimal medium, the level of aminoacyl-tRNAs is more uniform and rises to approximately 60\%. Particularly, the charging level of tRNA(Ser), tRNA(Cys), tRNA(Thr) and tRNA(His) is below 50\% in complex medium and their aminoacylation levels mirror the degree that amino acids inhibit growth when individually added to minimal medium. Serine is among the most toxic amino acids for bacteria and tRNAs(Ser) exhibit the lowest charging levels, below 10\%, at high growth rate although intracellular serine concentration is plentiful. As a result some serine codons are among the most slowly translated codons. A large fraction of the serine is most likely degraded by L-serine-deaminase, which competes with the seryl-tRNA-synthetase that charges the tRNAs(Ser). These results indicate that the level of aminoacylation in complex media might be a competition between charging for translation and degradation of amino acids that inhibit growth.},
  language  = {en}
}
@misc{LukoszekFeistIgnatova2016,
  author    = {Lukoszek, Radoslaw and Feist, Peter and Ignatova, Zoya},
  title     = {Insights into the adaptive response of Arabidopsis thaliana to prolonged thermal stress by ribosomal profiling and RNA-Seq},
  series = {BMC plant biology},
  journal   = {BMC plant biology},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407262},
  pages     = {13},
  year      = {2016},
  abstract  = {Background: Environmental stress puts organisms at risk and requires specific stress-tailored responses to maximize survival. Long-term exposure to stress necessitates a global reprogramming of the cellular activities at different levels of gene expression. Results: Here, we use ribosome profiling and RNA sequencing to globally profile the adaptive response of Arabidopsis thaliana to prolonged heat stress. To adapt to long heat exposure, the expression of many genes is modulated in a coordinated manner at a transcriptional and translational level. However, a significant group of genes opposes this trend and shows mainly translational regulation. Different secondary structure elements are likely candidates to play a role in regulating translation of those genes. Conclusions: Our data also uncover on how the subunit stoichiometry of multimeric protein complexes in plastids is maintained upon heat exposure.},
  language  = {en}
}
@article{LukoszekFeistIgnatova2016,
  author    = {Lukoszek, Radoslaw and Feist, Peter and Ignatova, Zoya},
  title     = {Insights into the adaptive response of Arabidopsis thaliana to prolonged thermal stress by ribosomal profiling and RNA-Seq},
  series = {BMC plant biology},
  volume    = {16},
  journal   = {BMC plant biology},
  publisher = {BioMed Central},
  address   = {London},
  issn      = {1471-2229},
  doi       = {10.1186/s12870-016-0915-0},
  pages     = {13},
  year      = {2016},
  abstract  = {Background: Environmental stress puts organisms at risk and requires specific stress-tailored responses to maximize survival. Long-term exposure to stress necessitates a global reprogramming of the cellular activities at different levels of gene expression. Results: Here, we use ribosome profiling and RNA sequencing to globally profile the adaptive response of Arabidopsis thaliana to prolonged heat stress. To adapt to long heat exposure, the expression of many genes is modulated in a coordinated manner at a transcriptional and translational level. However, a significant group of genes opposes this trend and shows mainly translational regulation. Different secondary structure elements are likely candidates to play a role in regulating translation of those genes. Conclusions: Our data also uncover on how the subunit stoichiometry of multimeric protein complexes in plastids is maintained upon heat exposure.},
  language  = {en}
}