Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation

Emma M Briggs, View ORCID ProfileKathryn Crouch, Leandro Lemgruber, Graham Hamilton, Craig Lapsley, View ORCID ProfileRichard McCulloch
doi: https://doi.org/10.1101/541300
Emma M Briggs
University of Glasgow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathryn Crouch
University of Glasgow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Kathryn Crouch
Leandro Lemgruber
University of Glasgow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Graham Hamilton
University of Glasgow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Craig Lapsley
University of Glasgow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard McCulloch
University of Glasgow
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Richard McCulloch
  • For correspondence: richard.mcculloch@glasgow.ac.uk
  • Abstract
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

In every cell ribonucleotides represent a threat to the stability and transmission of the DNA genome. Two types of Ribonuclease H (RNase H) tackle such ribonucleotides, either by excision when they form part of the DNA strand, or by hydrolysing RNA when it base-pairs with DNA, in structures termed R-loops. Loss of either RNase H is lethal in mammals, whereas yeast can prosper in the absence of both enzymes. Removal of RNase H1 is tolerated by the parasite Trypanosoma brucei but no work has examined the function of RNase H2. Here we show that loss of the catalytic subunit of T. brucei RNase H2 (TbRH2A) leads to growth and cell cycle arrest that is concomitant with accumulation of nuclear damage at sites of RNA polymerase (Pol) II transcription initiation, revealing a novel and critical role for RNase H2. In addition, differential gene expression of both RNA Pol I and II transcribed genes occurs after TbRH2A loss, including patterns that may relate to cytosolic DNA accumulation in humans with autoimmune disease. Finally, we show that TbRH2A loss causes R-loop and DNA damage accumulation in telomeric RNA Pol I transcription sites, leading to altered variant surface glycoprotein expression. Thus, we demonstrate a separation of function between the two nuclear T. brucei RNase H enzymes during RNA Pol II transcription, but overlap in function during RNA Pol I-mediated gene expression during host immune evasion.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted February 05, 2019.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
Share
Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation
Emma M Briggs, Kathryn Crouch, Leandro Lemgruber, Graham Hamilton, Craig Lapsley, Richard McCulloch
bioRxiv 541300; doi: https://doi.org/10.1101/541300
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Trypanosoma brucei ribonuclease H2A is an essential enzyme that resolves R-loops associated with transcription initiation and antigenic variation
Emma M Briggs, Kathryn Crouch, Leandro Lemgruber, Graham Hamilton, Craig Lapsley, Richard McCulloch
bioRxiv 541300; doi: https://doi.org/10.1101/541300

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (996)
  • Biochemistry (1485)
  • Bioengineering (938)
  • Bioinformatics (6803)
  • Biophysics (2414)
  • Cancer Biology (1782)
  • Cell Biology (2514)
  • Clinical Trials (106)
  • Developmental Biology (1683)
  • Ecology (2553)
  • Epidemiology (1488)
  • Evolutionary Biology (5003)
  • Genetics (3598)
  • Genomics (4614)
  • Immunology (1157)
  • Microbiology (4222)
  • Molecular Biology (1617)
  • Neuroscience (10744)
  • Paleontology (81)
  • Pathology (236)
  • Pharmacology and Toxicology (407)
  • Physiology (552)
  • Plant Biology (1445)
  • Scientific Communication and Education (410)
  • Synthetic Biology (542)
  • Systems Biology (1868)
  • Zoology (257)