State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
Department of Biochemistry, Universidad Autónoma de Madrid (UAM), Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain.
Front Immunol. 2022 May 12;13:861655. doi: 10.3389/fimmu.2022.861655. eCollection 2022.
A microRNA (miRNA) often regulates the expression of hundreds of target genes. A fundamental question in the field of miRNA research is whether a miRNA exerts its biological function through regulating a small number of key targets or through small changes in the expression of hundreds of target genes. We addressed this issue by performing functional analysis of target genes regulated by miR-148a. We previously identified miR-148a as a critical regulator of B cell central tolerance and found 119 target genes that may mediate its function. We selected 4 of them for validation and demonstrated a regulatory role for , , and in this process. In this study, we performed functional analysis of the other miR-148a target genes in and models of B cell central tolerance. Our results show that those additional target genes play a minimal role, if any, in miR-148a-mediated control of B cell central tolerance, suggesting that the function of miRNAs is mediated by a few key target genes. These findings have advanced our understanding of molecular mechanisms underlying miRNA regulation of gene expression and B cell central tolerance.
微小 RNA（miRNA）通常调节数百个靶基因的表达。miRNA 研究领域的一个基本问题是，miRNA 是通过调节少数关键靶基因，还是通过数百个靶基因的表达的微小变化来发挥其生物学功能。我们通过对 miR-148a 调节的靶基因进行功能分析来解决这个问题。我们之前发现 miR-148a 是 B 细胞中枢耐受的关键调节因子，并确定了 119 个可能介导其功能的靶基因。我们从中选择了 4 个进行验证，并证明了在这个过程中 、 和 的调节作用。在这项研究中，我们在 B 细胞中枢耐受的 和 模型中对其他 miR-148a 靶基因进行了功能分析。我们的结果表明，这些额外的靶基因在 miR-148a 介导的 B 细胞中枢耐受控制中作用很小，如果有的话，这表明 miRNA 的功能是由少数几个关键靶基因介导的。这些发现加深了我们对 miRNA 调控基因表达和 B 细胞中枢耐受的分子机制的理解。
