Evidence map›Paper›PMID 34402853›Full record

ArticleThe Journal of experimental medicine2021

The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination.

Helen A Beilinson, Rebecca A Glynn, Anurupa Devi Yadavalli, Jianxiong Xiao, Elizabeth Corbett, Huseyin Saribasak, Rahul Arya, Charline Miot, Anamika Bhattacharyya, Jessica M Jones and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  8. Review
  9. DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022
    Review
  10. Review
  11. Article
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

13 authors at 4 institutions in 2 countries.

Helen A BeilinsonDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT.ORCID 0000-0002-2888-5256
Rebecca A GlynnCell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.ORCID 0000-0002-3916-6900
Anurupa Devi YadavalliDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT.ORCID 0000-0003-4733-8028
Jianxiong XiaoDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT.ORCID 0000-0002-7263-0226
Elizabeth CorbettDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT.ORCID 0000-0003-4825-0415
Huseyin SaribasakDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT.ORCID 0000-0003-0055-062X
Rahul AryaDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.ORCID 0000-0003-0867-6585
Charline MiotDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.ORCID 0000-0002-4586-1061
Anamika BhattacharyyaDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC.ORCID 0000-0001-8858-3308
Jessica M JonesDepartment of Biochemistry and Molecular & Cellular Biology, Georgetown University, Washington, DC.ORCID 0000-0002-0380-1183
Jagan M R PongubalaDepartment of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.ORCID 0000-0003-3001-9872
Craig H BassingCell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.ORCID 0000-0003-1703-0786
David G SchatzDepartment of Immunobiology, Yale School of Medicine, Yale University, New Haven, CT.ORCID 0000-0002-5669-1176
Yale University · USChildren's Hospital of Philadelphia · USGeorgetown University · USUniversity of Hyderabad · IN

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
INTERDISCIPLINARY IMMUNOLOGY TRAINING PROGRAMT32AI007019 · NIAID · YALE UNIVERSITY · PI Carrie L. Lucas, David G. Schatz · 1985 to 2026
$14.4M
TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
Mechanism and Targeting of V(D)J RecombinationR01AI032524 · NIAID · YALE UNIVERSITY · PI David G. Schatz · 1992 to 2026
$6.7M
DNA Double Strand Break Mediated Feedback Inhibition of V(D)J RecombinationR01AI112621 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSING, CRAIG H · 2015 to 2019
$1.9M
Exploring the Role of RAG1 in Post-transcriptional Gene RegulationR21AI135435 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI BASSING, CRAIG H · 2019 to 2020
$484k
NCATS NIH HHS UL1 TR001863NIAID NIH HHS R01 AI032524NIAID NIH HHS R01 AI112621NIAID NIH HHS R21 AI135435NIAID NIH HHS T32 AI007019NIGMS NIH HHS T32 GM007229NIH HHS R01 AI032524NIH HHS T32 AI-007019NIH HHS T32 GM-07229
6 · The paper itself

Abstract

Immunoglobulin and T cell receptor gene assembly depends on V(D)J recombination initiated by the RAG1-RAG2 recombinase. The RAG1 N-terminal region (NTR; aa 1-383) has been implicated in regulatory functions whose influence on V(D)J recombination and lymphocyte development in vivo is poorly understood. We generated mice in which RAG1 lacks ubiquitin ligase activity (P326G), the major site of autoubiquitination (K233R), or its first 215 residues (Δ215). While few abnormalities were detected in R1.K233R mice, R1.P326G mice exhibit multiple features indicative of reduced recombination efficiency, including an increased Igκ+:Igλ+ B cell ratio and decreased recombination of Igh, Igκ, Igλ, and Tcrb loci. Previous studies indicate that synapsis of recombining partners during Igh recombination occurs through two pathways: long-range scanning and short-range collision. We find that R1Δ215 mice exhibit reduced short-range Igh and Tcrb D-to-J recombination. Our findings indicate that the RAG1 NTR regulates V(D)J recombination and lymphocyte development by multiple pathways, including control of the balance between short- and long-range recombination.

Indexed as

AnimalsB-LymphocytesFemaleHomeodomain ProteinsImmunoglobulinsLymphocytesMaleMiceMice, Mutant StrainsProtein Serine-Threonine KinasesProto-Oncogene ProteinsT-Lymphocyte SubsetsUbiquitinationUbiquitin-Protein LigasesV(D)J RecombinationHomeodomain ProteinsIgKImmunoglobulinsPim2 protein, mouseProtein Serine-Threonine KinasesProto-Oncogene ProteinsRAG-1 proteinUbiquitin-Protein Ligases

Identifiers

PMID34402853
PMCPMC8374863
OpenAlexW3196221672

What Socratic holds

Textmetadata
LicenceCC BY-NC-SA
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.