Evidence map›Paper›PMID 34644584›Full record

ArticleCell reports2021

RAG2 abolishes RAG1 aggregation to facilitate V(D)J recombination.

Tingting Gan, Yuhong Wang, Yang Liu, David G Schatz, Jiazhi Hu

Open access · goldAbstract readComparative Study
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 30 citations in OpenAlex.

  1. A Synthetic Platform for Antibody Junctional Diversification Beyond Natural Constraints.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  13. DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022
    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

5 authors at 2 institutions in 2 countries.

Tingting GanThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Yuhong WangThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
Yang LiuThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
David G SchatzDepartment of Immunobiology, Yale University School of Medicine, New Haven, CT 06519, USA.
Jiazhi HuThe MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China. Electronic address: hujz@pku.edu.cn.
Peking University · CNYale University · US

Funding

Mechanism and Targeting of V(D)J RecombinationR01AI032524 · NIAID · YALE UNIVERSITY · PI David G. Schatz · 1992 to 2026
$6.7M
Immunoglobulin and T Cell Receptor Gene AssemblyR37AI032524 · NIAID · YALE UNIVERSITY · PI SCHATZ, DAVID G. · 2007 to 2016
$3.5M
NIAID NIH HHS R01 AI032524NIAID NIH HHS R37 AI032524
6 · The paper itself

Abstract

RAG1 and RAG2 form a tetramer nuclease to initiate V(D)J recombination in developing T and B lymphocytes. The RAG1 protein evolves from a transposon ancestor and possesses nuclease activity that requires interaction with RAG2. Here, we show that the human RAG1 aggregates in the nucleus in the absence of RAG2, exhibiting an extremely low V(D)J recombination activity. In contrast, RAG2 does not aggregate by itself, but it interacts with RAG1 to disrupt RAG1 aggregates and thereby activate robust V(D)J recombination. Moreover, RAG2 from mouse and zebrafish could not disrupt the aggregation of human RAG1 as efficiently as human RAG2 did, indicating a species-specific regulatory mechanism for RAG1 by RAG2. Therefore, we propose that RAG2 coevolves with RAG1 to release inert RAG1 from aggregates and thereby activate V(D)J recombination to generate diverse antigen receptors in lymphocytes.

Indexed as

G1 PhaseV(D)J RecombinationCell Line, TumorCell Nucleus StructuresDNA-Binding ProteinsHEK293 CellsHomeodomain ProteinsHumansLymphocytesNuclear ProteinsProtein AggregatesSpecies SpecificityZebrafish ProteinsDNA-Binding ProteinsHomeodomain ProteinsNuclear ProteinsProtein AggregatesRAG-1 proteinRAG2 protein, humanRag2 protein, mouseRAG2 protein, zebrafishZebrafish ProteinsB lymphocytesProtein aggregationRAG complexV(D)J recombination

Identifiers

PMID34644584
PMCPMC8783374
OpenAlexW3198813442

What OpenQuestion holds

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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.