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

IF 4.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Journal Pub Date : 2023-12-20 DOI:10.1042/bcj20230250
Kumari, Rupa, Roy, Urbi, Desai, Sagar, Mondal, Arannya S., Nair, Rajshree R., Nilavar, Namrata, Choudhary, Bibha, Raghavan, Sathees C.
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Abstract

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.
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微RNA、miR-501调控B细胞中的V(D)J重组
RAGs(重组激活基因)是负责 V(D)J 重组的位点特异性内切酶,严格调控 RAGs 对防止淋巴细胞中的基因组重排和染色体易位非常重要。在本研究中,我们发现了一种能调节淋巴细胞中 RAG1 表达的 microRNA,即 miR-501。过量表达前 miRNA 构建物会导致成熟 miRNA 的产生,同时降低 RAG1 的表达,而使用抗 miRs 抑制则会导致其表达增强。报告实验证实了 miR-501 的 3′UTR 与 RAG1 的直接相互作用。重要的是,miRNAs 的过度表达导致抑制了 B 细胞中的 V(D)J 重组,揭示了它们对 RAGs 生理功能的影响。值得关注的是,在各种白血病患者和淋巴细胞系中观察到 miR-501 与 RAG1 呈反相关,这表明它可能用于癌症治疗。因此,我们的研究结果揭示了 miR-501-3p 在 B 细胞中对 RAG1 的调控,从而揭示了 V(D)J 重组及其对免疫球蛋白白血病发生的可能影响。
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来源期刊
Biochemical Journal
Biochemical Journal 生物-生化与分子生物学
CiteScore
8.00
自引率
0.00%
发文量
255
审稿时长
1 months
期刊介绍: Exploring the molecular mechanisms that underpin key biological processes, the Biochemical Journal is a leading bioscience journal publishing high-impact scientific research papers and reviews on the latest advances and new mechanistic concepts in the fields of biochemistry, cellular biosciences and molecular biology. The Journal and its Editorial Board are committed to publishing work that provides a significant advance to current understanding or mechanistic insights; studies that go beyond observational work using in vitro and/or in vivo approaches are welcomed. Painless publishing: All papers undergo a rigorous peer review process; however, the Editorial Board is committed to ensuring that, if revisions are recommended, extra experiments not necessary to the paper will not be asked for. Areas covered in the journal include: Cell biology Chemical biology Energy processes Gene expression and regulation Mechanisms of disease Metabolism Molecular structure and function Plant biology Signalling
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