@misc{GorochowskiIgnatovaBovenbergetal.2015,
  author    = {Gorochowski, Thomas E. and Ignatova, Zoya and Bovenberg, Roel A. L. and Roubos, Johannes A.},
  title     = {Trade-offs between tRNA abundance and mRNA secondary structure support smoothing of translation elongation rate},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {816},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-44134},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-441340},
  pages     = {13},
  year      = {2015},
  abstract  = {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.},
  language  = {en}
}
@misc{ZurnicHuetterRzehaetal.2016,
  author    = {Zurnic, Irena and H{\"u}tter, Sylvia and Rzeha, Ute and Stanke, Nicole and Reh, Juliane and M{\"u}llers, Erik and Hamann, Martin V. and Kern, Tobias and Gerresheim, Gesche K. and Lindel, Fabian and Serrao, Erik and Lesbats, Paul and Engelman, Alan N. and Cherepanov, Peter and Lindemann, Dirk},
  title     = {Interactions of prototype foamy virus capsids with host cell polo-like kinases are important for efficient viral DNA integration},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe},
  number    = {580},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-41131},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-411317},
  pages     = {36},
  year      = {2016},
  abstract  = {Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.},
  language  = {en}
}