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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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MiR-23~27~24 clusters control effector T cell differentiation and function

ABSTRACT: Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, here we show that the miR-23~27~24 clusters regulate multiple aspects of T cell biology, particularly Th2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23~27~24 clusters revealed miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, while overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17 and iTreg cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest tight regulation of miR-23~27~24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses. naÃ¯ve T cells isolated from mice with T cell-specific overexpression of the entire miR-23 cluster or individual miR-23 family members as well as from mice with T cell-specific deletion of both miR-23a/b clusters

ORGANISM(S): Mus musculus

SUBMITTER: Aly Khan

PROVIDER: E-GEOD-75909 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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miR-23~27~24 clusters control effector T cell differentiation and function

Project description:Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, here we show that the miR-23~27~24 clusters regulate multiple aspects of T cell biology, particularly Th2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23~27~24 clusters revealed miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, while overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17 and iTreg cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest tight regulation of miR-23~27~24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses.

2015-12-11 | GSE75909 | GEO

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Mus musculus

Project description:miR-23~27~24 clusters control effector T cell differentiation and function

| PRJNA305697 | ENA

Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans [RNA-Seq]

2015-06-05 | GSE60420 | GEO

Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans [miRNA-Seq]

2015-06-05 | GSE60419 | GEO

Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans [miRNA-Seq]

Project description:In animals, microRNAs frequently form families with related sequences. The functional relevance of miRNA families and the relative contribution of family members to target repression have remained, however, largely unexplored. Here, we used the C. elegans miR-58 miRNA family, comprised primarily of four highly abundant members: miR-58.1, miR-80, miR-81 and miR-82, as a model to investigate the redundancy of miRNA family members and their impact on target expression in an in vivo setting. RNA was extracted from different miR-58 family mutants (mir-58.1, mir-80; mir-58.1 and mir-80; mir-58.1; mir-81-82) and wild-type Bristol C. elegans strain at late L4 stage and submitted to small RNA profiling with Illumina HiSeq2000. The goal was to see whether miR-58 family members can compensate each other's expression.

2015-06-05 | E-GEOD-60419 | biostudies-arrayexpress

Cooperative target mRNA destabilization and translation inhibition by miR-58 microRNA family in C. elegans [RNA-Seq]

Project description:In animals, microRNAs frequently form families with related sequences. The functional relevance of miRNA families and the relative contribution of family members to target repression have remained, however, largely unexplored. Here, we used the C. elegans miR-58 miRNA family, comprised primarily of four highly abundant members: miR-58.1, miR-80, miR-81 and miR-82, as a model to investigate the redundancy of miRNA family members and their impact on target expression in an in vivo setting. RNA was extracted from different miR-58 family mutants (mir-58.1, mir-80; mir-58.1 and mir-80; mir-58.1; mir-81-82) and wild-type Bristol C. elegans strain at late L4 stage and submitted to transcriptome sequencing with Illumina HiSeq2000. The goal was to compare miR-58 target RNA expression and system-wide perturbations across various samples.

2015-06-05 | E-GEOD-60420 | biostudies-arrayexpress

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