AUTHOR=Ma Fengge , Zhan Yating , Bartolomé-Cabrero Rocío , Ying Wei , Asano Masahide , Huang Zhe , Xiao Changchun , González-Martín Alicia 

TITLE=Analysis of a miR-148a Targetome in B Cell Central Tolerance

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.861655

DOI=10.3389/fimmu.2022.861655

ISSN=1664-3224

ABSTRACT=<p>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 <italic>Bim</italic>, <italic>Pten</italic>, and <italic>Gadd45a</italic> in this process. In this study, we performed functional analysis of the other miR-148a target genes in <italic>in vitro</italic> and <italic>in vivo</italic> 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.</p>