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.

中文翻译：

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MicroRNA、miR-501 调节 B 细胞中的 V(D)J 重组

RAG（重组激活基因）是负责 V(D)J 重组的位点特异性核酸内切酶，其严格调控对于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，我们鉴定了一种微小RNA，miR-501，它可以调节淋巴细胞中RAG1的表达。 pre-miRNA 构建体的过度表达导致成熟 miRNA 的生成，并伴随着 RAG1 表达的减少，而使用抗 miR 的抑制导致其表达增强。报告基因检测证实了 miR-501 的 3'UTR 与 RAG1 的直接相互作用。重要的是，miRNA 的过度表达导致 B 细胞中 V(D)J 重组的抑制，揭示了它们对 RAG 生理功能的影响。令人感兴趣的是在各种白血病患者和淋巴细胞系中观察到 miR-501 与 RAG1 呈负相关，这表明其在癌症治疗中的可能用途。因此，我们的结果揭示了 B 细胞中 miR-501-3p 对 RAG1 的调节以及 V(D)J 重组及其对免疫球蛋白白血病发生的可能影响。