Evidence map›Paper›PMID 28065739›Full record

ArticleJournal of molecular biology2017

R-Loop Depletion by Over-expressed RNase H1 in Mouse B Cells Increases Activation-Induced Deaminase Access to the Transcribed Strand without Altering Frequency of Isotype Switching.

Robert W Maul, Hyongi Chon, Kiran Sakhuja, Susana M Cerritelli, Lina A Gugliotti, Patricia J Gearhart, Robert J Crouch

Abstract read
In one paragraph

Article in Journal of molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

18 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. HumanmicroPublication biology · 2024
    Article
  7. p53-dependent R-loop formation and HPV pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. Article
  9. RNase H1, the Gold Standard for R-Loop Detection.Methods in molecular biology (Clifton, N.J.) · 2022
    Review
  10. Review
  11. Article
  12. Review
  13. Review
  14. Current insights into the mechanism of mammalian immunoglobulin class switch recombination.Critical reviews in biochemistry and molecular biology · 2019
    Review
  15. Article
  16. Article
  17. Review
  18. 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

7 authors at 2 institutions in 1 country.

Robert W MaulLaboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Hyongi ChonDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Kiran SakhujaDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Susana M CerritelliDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Lina A GugliottiDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Patricia J GearhartLaboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA. Electronic address: gearhartp@mail.nih.gov.
Robert J CrouchDivision of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA. Electronic address: crouchr@helix.nih.gov.
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USNational Institutes of Health · US

Funding

Factors Influencing Genetic Transcription Initiation And TerminationZIAHD000068 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI CROUCH, ROBERT J · 2009 to 2025
$22.0M
Roles for Transcription in Antibody DiversityZIAAG000714 · NIA · NATIONAL INSTITUTE ON AGING · PI GEARHART, PATRICIA J · 2009 to 2025
$10.9M
Roles for Transcription in Antibody DiversityZ01AG000714 · NIA · NATIONAL INSTITUTE ON AGING · PI GEARHART, PATRICIA J · 1988 to 2008
$319k
Intramural NIH HHS Z01 AG000714
6 · The paper itself

Abstract

R-loops, three-strand structures consisting of mRNA hybridized to the complementary DNA and a single-stranded DNA loop, are formed in switch regions on the heavy-chain immunoglobulin locus. To determine if R-loops have a direct effect on any of the steps involved in isotype switching, we generated a transgenic mouse that over-expressed RNase H1, an enzyme that cleaves the RNA of RNA/DNA hybrids in B cells. R-loops in the switch μ region were depleted by 70% in ex vivo activated splenic B cells. Frequencies of isotype switching to IgG1, IgG2b, IgG2c, and IgG3 were the same as C57BL/6 control cells. However, somatic hypermutation was increased specifically on the transcribed strand from μ-γ joins, indicating that R-loops limit activation-induced (cytosine) deaminase access to the transcribed DNA strand. Our data suggest that, in the normal G+C-rich context of mammalian class switch recombination regions, R-loops are obligatory intermediates. Processing of the R-loops is needed to remove RNA allowing activation-induced (cytosine) deaminase to promote somatic hypermutation on both DNA strands to generate double-strand DNA breaks for efficient class switch recombination. One of the two cellular RNases H may assist in this process.

Indexed as

Nucleic Acid ConformationRecombination, GeneticAICDA (Activation-Induced Cytidine Deaminase)AnimalsB-LymphocytesCytidine DeaminaseDNA Breaks, Double-StrandedFemaleImmunoglobulin Class SwitchingImmunoglobulin IsotypesMaleMiceMice, Inbred C57BLMice, TransgenicRibonuclease HSomatic Hypermutation, ImmunoglobulinAICDA (Activation-Induced Cytidine Deaminase)Cytidine DeaminaseImmunoglobulin IsotypesRibonuclease Hribonuclease HIclass switch recombinationR-loopsRNase H1somatic hypermutationtransgenic mouse

Identifiers

PMID28065739
PMCPMC5500445
OpenAlexW2570857957

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.