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

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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.
Tijdschrift: Cell Reports
ISSN: 2211-1247
Issue: 2
Volume: 36
Jaar van publicatie:2021
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:3
CSS-citation score:1
Auteurs:International
Authors from:Higher Education
Toegankelijkheid:Open