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Nucleic Acids Res. 2014 Sep;42(15):9717-29. doi: 10.1093/nar/gku714. Epub 2014 Aug 7.

Regulation of transcription termination by glucosylated hydroxymethyluracil, base J, in Leishmania major and Trypanosoma brucei.

Author information

  • 1Department of Biochemistry and Molecular Biology, University of Georgia, Davison Life Sciences Building, 120 Green Street, Athens, GA 30602-7229, USA.
  • 2Core Unit Systems Medicine, University of Wuerzburg, Wuerzburg 97080, Germany.
  • 3Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, Département Biologie cellulaire et infection, Paris 75015, France INSERM U786, Paris 75015, France.
  • 4Research Center for Infectious Diseases, University of Wuerzburg, Wuerzburg 97080, Germany.
  • 5Department of Biochemistry and Molecular Biology, University of Georgia, Davison Life Sciences Building, 120 Green Street, Athens, GA 30602-7229, USA rsabatini@bmb.uga.edu.

Abstract

Base J, β-d-glucosyl-hydroxymethyluracil, is an epigenetic modification of thymine in the nuclear DNA of flagellated protozoa of the order Kinetoplastida. J is enriched at sites involved in RNA polymerase (RNAP) II initiation and termination. Reduction of J in Leishmania tarentolae via growth in BrdU resulted in cell death and indicated a role of J in the regulation of RNAP II termination. To further explore J function in RNAP II termination among kinetoplastids and avoid indirect effects associated with BrdU toxicity and genetic deletions, we inhibited J synthesis in Leishmania major and Trypanosoma brucei using DMOG. Reduction of J in L. major resulted in genome-wide defects in transcription termination at the end of polycistronic gene clusters and the generation of antisense RNAs, without cell death. In contrast, loss of J in T. brucei did not lead to genome-wide termination defects; however, the loss of J at specific sites within polycistronic gene clusters led to altered transcription termination and increased expression of downstream genes. Thus, J regulation of RNAP II transcription termination genome-wide is restricted to Leishmania spp., while in T. brucei it regulates termination and gene expression at specific sites within polycistronic gene clusters.

PMID:
25104019
PMCID:
PMC4150806
DOI:
10.1093/nar/gku714
[PubMed - indexed for MEDLINE]
Free PMC Article
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