MicroRNA, miR-501 regulate the V(D)J recombination in B cells.

The stringent regulation of RAGs (Recombination activating genes), the site-specific endonuclease responsible for V(D)J recombination, is important to prevent genomic rearrangements and chromosomal translocations in lymphoid cells. In the present study, we identify a microRNA, miR-501, which can regulate the expression of RAG1 in lymphoid cells. Overexpression of the pre-miRNA construct led to the generation of mature miRNAs and a concomitant reduction in RAG1 expression, whereas inhibition using anti-miRs resulted in its enhanced expression. The direct interaction of the 3'UTR of miR-501 with RAG1 was confirmed by the reporter assay. Importantly, overexpression of miRNAs led to inhibition of V(D)J recombination in B cells, revealing their impact on the physiological function of RAGs. Of interest is the inverse correlation observed for miR-501 with RAG1 in various leukemia patients and lymphoid cell lines, suggesting its possible use in cancer therapy. Thus, our results reveal the regulation of RAG1 by miR-501-3p in B cells and thus V(D)J recombination and its possible implications on immunoglobulin leukemogenesis. © 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Citation

Rupa Kumari, Urbi Roy, Sagar Desai, Arannya S Mondal, Rajshree R Nair, Namrata Nilavar, Bibha Choudhary, Sathees C Raghavan. MicroRNA, miR-501 regulate the V(D)J recombination in B cells. The Biochemical journal. 2023 Dec 20;480(24):2061-2077

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PMID: 38084601

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