@article{ReynoldsHofmeisterCliffeetal.2016,
  author    = {Reynolds, David and Hofmeister, Brigitte T. and Cliffe, Laura and Alabady, Magdy and Siegel, T. Nicolai and Schmitz, Robert J. and Sabatini, Robert},
  title     = {Histone H3 Variant Regulates RNA Polymerase II Transcription Termination and Dual Strand Transcription of siRNA Loci in Trypanosoma brucei},
  series = {PLoS Genetics},
  volume    = {12},
  journal   = {PLoS Genetics},
  number    = {1},
  doi       = {10.1371/journal.pgen.1005758},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166738},
  pages     = {e1005758},
  year      = {2016},
  abstract  = {Base J, β-D-glucosyl-hydroxymethyluracil, is a chromatin modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida. In Trypanosoma brucei, J is enriched, along with histone H3 variant (H3.V), at sites involved in RNA Polymerase (RNAP) II termination and telomeric sites involved in regulating variant surface glycoprotein gene (VSG) transcription by RNAP I. Reduction of J in T. brucei indicated a role of J in the regulation of RNAP II termination, where the loss of J at specific sites within polycistronic gene clusters led to read-through transcription and increased expression of downstream genes. We now demonstrate that the loss of H3.V leads to similar defects in RNAP II termination within gene clusters and increased expression of downstream genes. Gene derepression is intensified upon the subsequent loss of J in the H3.V knockout. mRNA-seq indicates gene derepression includes VSG genes within the silent RNAP I transcribed telomeric gene clusters, suggesting an important role for H3.V in telomeric gene repression and antigenic variation. Furthermore, the loss of H3.V at regions of overlapping transcription at the end of convergent gene clusters leads to increased nascent RNA and siRNA production. Our results suggest base J and H3.V can act independently as well as synergistically to regulate transcription termination and expression of coding and non-coding RNAs in T. brucei, depending on chromatin context (and transcribing polymerase). As such these studies provide the first direct evidence for histone H3.V negatively influencing transcription elongation to promote termination.},
  language  = {en}
}
@article{KramerPiperEstevezetal.2016,
  author    = {Kramer, Susanne and Piper, Sophie and Estevez, Antonio and Carrington, Mark},
  title     = {Polycistronic trypanosome mRNAs are a target for the exosome},
  series = {Molecular and Biochemical Parasitology},
  volume    = {205},
  journal   = {Molecular and Biochemical Parasitology},
  number    = {1-2},
  doi       = {10.1016/j.molbiopara.2016.02.009},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191350},
  pages     = {1-5},
  year      = {2016},
  abstract  = {Eukaryotic cells have several mRNA quality control checkpoints to avoid the production of aberrant proteins. Intron-containing mRNAs are actively degraded by the nuclear exosome, prevented from nuclear exit and, if these systems fail, degraded by the cytoplasmic NMD machinery. Trypanosomes have only two introns. However, they process mRNA5 from long polycistronic precursors by trans-splicing and polycistronic mRNA molecules frequently arise from any missed splice site. Here, we show that RNAi depletion of the trypanosome exosome, but not of the cytoplasmic 5'-3' exoribonuclease XRNA or the NMD helicase UPF1, causes accumulation of oligocistronic mRNA5. We have also revisited the localization of the trypanosome exosome by expressing eYFP-fusion proteins of the exosome subunits RRP44 and RRP6. Both proteins are significantly enriched in the nucleus. Together with published data, our data suggest a major nuclear function of the trypanosome exosome in rRNA, snoRNA and mRNA quality control.},
  language  = {en}
}
@article{CicovaDejungSkalickyetal.2016,
  author    = {Cicova, Zdenka and Dejung, Mario and Skalicky, Tomas and Eisenhuth, Nicole and Hanselmann, Steffen and Morriswood, Brooke and Figueiredo, Luisa M. and Butter, Falk and Janzen, Christian J.},
  title     = {Two flagellar BAR domain proteins in Trypanosoma brucei with stage-specific regulation},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  doi       = {10.1038/srep35826},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181021},
  year      = {2016},
  abstract  = {Trypanosomes are masters of adaptation to different host environments during their complex life cycle. Large-scale proteomic approaches provide information on changes at the cellular level, and in a systematic way. However, detailed work on single components is necessary to understand the adaptation mechanisms on a molecular level. Here, we have performed a detailed characterization of a bloodstream form (BSF) stage-specific putative flagellar host adaptation factor Tb927.11.2400, identified previously in a SILAC-based comparative proteome study. Tb927.11.2400 shares 38\% amino acid identity with TbFlabarin (Tb927.11.2410), a procyclic form (PCF) stage-specific flagellar BAR domain protein. We named Tb927.11.2400 TbFlabarin-like (TbFlabarinL), and demonstrate that it originates from a gene duplication event, which occurred in the African trypanosomes. TbFlabarinL is not essential for the growth of the parasites under cell culture conditions and it is dispensable for developmental differentiation from BSF to the PCF in vitro. We generated TbFlabarinL-specific antibodies, and showed that it localizes in the flagellum. Co-immunoprecipitation experiments together with a biochemical cell fractionation suggest a dual association of TbFlabarinL with the flagellar membrane and the components of the paraflagellar rod.},
  language  = {en}
}