4.8 Article

MicroRNA miR-29c regulates RAG1 expression and modulates V(D)J recombination during B cell development

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CELL REPORTS
卷 36, 期 2, 页码 -

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CELL PRESS
DOI: 10.1016/j.celrep.2021.109390

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资金

  1. DBT, India [BT/PR13616/GET/119/9/2015, BT/PR13458/COE/34/33/2015]
  2. IISc-DBT partnership program [DBT/BF/PR/INS/2011-12/IISc]
  3. Senior Research fellowships from DBT
  4. CSIR, India
  5. IISc

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The study showed that miR-29c regulates RAG1 in a B cell stage-specific manner, modulation of miR-29c levels affects V(D)J recombination efficiency in pre-B cells, and a negative correlation between miR-29c and RAG1 levels is observed in different developmental stages.
Recombination activating genes (RAGs), consisting of RAG1 and RAG2, are stringently regulated lymphoid-specific genes, which initiate V(D)J recombination in developing lymphocytes. We report the regulation of RAG1 through a microRNA (miRNA), miR-29c, in a B cell stage-specific manner in mice and humans. Various lines of experimentation, including CRISPR-Cas9 genome editing, demonstrate the target specificity and direct interaction of miR-29c to RAG1. Modulation of miR-29c levels leads to change in V(D)J recombination efficiency in pre-B cells. The miR-29c expression is inversely proportional to RAG1 in a B cell developmental stage-specific manner, and miR-29c null mice exhibit a reduction in mature B cells. A negative correlation of miR-29c and RAG1 levels is also observed in leukemia patients, suggesting the potential use of miR-29c as a biomarker and a therapeutic target. Thus, our results reveal the role of miRNA in the regulation of RAG1 and its relevance in cancer.

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