Evidence map›Paper›PMID 31350892›Full record

ArticleNucleic acids research2019

Trypanosoma brucei ribonuclease H2A is an essential R-loop processing enzyme whose loss causes DNA damage during transcription initiation and antigenic variation.

Emma Briggs, Kathryn Crouch, Leandro Lemgruber, Graham Hamilton, Craig Lapsley, Richard McCulloch

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. RAD51-mediated R-loop formation acts to repair transcription-associated DNA breaks driving antigenic variation inProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. A systematic analysis ofGenome research · 2021
    Article
  10. Review
  11. Review
  12. Article
  13. Regulation of Antigenic Variation byPathogens (Basel, Switzerland) · 2021
    Review
  14. Article
  15. Unpicking the Roles of DNA Damage Protein Kinases in Trypanosomatids.Frontiers in cell and developmental biology · 2021
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Emma BriggsThe Wellcome Centre for Integrative Parasitology, University of Glasgow, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Kathryn CrouchThe Wellcome Centre for Integrative Parasitology, University of Glasgow, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Leandro LemgruberThe Wellcome Centre for Integrative Parasitology, University of Glasgow, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Graham HamiltonGlasgow Polyomics, University of Glasgow, Wolfson Wohl Cancer Research Centre, Garscube Estate, Switchback Rd, Bearsden G61 1QH, UK.
Craig LapsleyThe Wellcome Centre for Integrative Parasitology, University of Glasgow, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Richard McCullochThe Wellcome Centre for Integrative Parasitology, University of Glasgow, College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, Sir Graeme Davies Building, 120 University Place, Glasgow G12 8TA, UK.
Wellcome Centre for Molecular Parasitology · GBUniversity of Glasgow · GB

Funding

Biotechnology and Biological Sciences Research Council BB/K006495/1Biotechnology and Biological Sciences Research Council BB/M028909/1Biotechnology and Biological Sciences Research Council BB/N016165/1Wellcome Trust 104111
6 · The paper itself

Abstract

Ribonucleotides represent a threat to DNA genome stability and transmission. Two types of Ribonuclease H (RNase H) excise ribonucleotides when they form part of the DNA strand, or hydrolyse RNA when it base-pairs with DNA in structures termed R-loops. Loss of either RNase H is lethal in mammals, whereas yeast survives the absence of both enzymes. RNase H1 loss is tolerated by the parasite Trypanosoma brucei but no work has examined the function of RNase H2. Here we show that loss 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. Differential gene expression analysis reveals limited overall changes in RNA levels for RNA Pol II genes after TbRH2A loss, but increased perturbation of nucleotide metabolic genes. Finally, we show that TbRH2A loss causes R-loop and DNA damage accumulation in telomeric RNA Pol I transcription sites, also leading to altered gene expression. Thus, we demonstrate separation of function between 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.

Indexed as

Transcription Initiation, GeneticAnimalsAntigens, ProtozoanDNADNA DamageDNA ReplicationGene Expression RegulationGenomic InstabilityHumansNucleic Acid ConformationRibonuclease HRNARNA Polymerase IRNA Polymerase IITrypanosoma brucei bruceiAntigens, ProtozoanDNARibonuclease Hribonuclease HIribonuclease HIIRNARNA Polymerase IRNA Polymerase II

Identifiers

PMID31350892
PMCPMC6753483
OpenAlexW2966688313

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.