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

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 gen...

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Autores principales: Ma, Fengge, Zhan, Yating, Bartolomé-Cabrero, Rocío, Ying, Wei, Asano, Masahide, Huang, Zhe, Xiao, Changchun, González-Martín, Alicia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134011/
https://www.ncbi.nlm.nih.gov/pubmed/35634349
http://dx.doi.org/10.3389/fimmu.2022.861655
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author Ma, Fengge
Zhan, Yating
Bartolomé-Cabrero, Rocío
Ying, Wei
Asano, Masahide
Huang, Zhe
Xiao, Changchun
González-Martín, Alicia
author_facet Ma, Fengge
Zhan, Yating
Bartolomé-Cabrero, Rocío
Ying, Wei
Asano, Masahide
Huang, Zhe
Xiao, Changchun
González-Martín, Alicia
author_sort Ma, Fengge
collection PubMed
description 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 Bim, Pten, and Gadd45a in this process. In this study, we performed functional analysis of the other miR-148a target genes in in vitro and in vivo 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.
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spelling pubmed-91340112022-05-27 Analysis of a miR-148a Targetome in B Cell Central Tolerance Ma, Fengge Zhan, Yating Bartolomé-Cabrero, Rocío Ying, Wei Asano, Masahide Huang, Zhe Xiao, Changchun González-Martín, Alicia Front Immunol Immunology 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 Bim, Pten, and Gadd45a in this process. In this study, we performed functional analysis of the other miR-148a target genes in in vitro and in vivo 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. Frontiers Media S.A. 2022-05-12 /pmc/articles/PMC9134011/ /pubmed/35634349 http://dx.doi.org/10.3389/fimmu.2022.861655 Text en Copyright © 2022 Ma, Zhan, Bartolomé-Cabrero, Ying, Asano, Huang, Xiao and González-Martín https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ma, Fengge
Zhan, Yating
Bartolomé-Cabrero, Rocío
Ying, Wei
Asano, Masahide
Huang, Zhe
Xiao, Changchun
González-Martín, Alicia
Analysis of a miR-148a Targetome in B Cell Central Tolerance
title Analysis of a miR-148a Targetome in B Cell Central Tolerance
title_full Analysis of a miR-148a Targetome in B Cell Central Tolerance
title_fullStr Analysis of a miR-148a Targetome in B Cell Central Tolerance
title_full_unstemmed Analysis of a miR-148a Targetome in B Cell Central Tolerance
title_short Analysis of a miR-148a Targetome in B Cell Central Tolerance
title_sort analysis of a mir-148a targetome in b cell central tolerance
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134011/
https://www.ncbi.nlm.nih.gov/pubmed/35634349
http://dx.doi.org/10.3389/fimmu.2022.861655
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