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Altered expression and editing of miRNA-100 regulates iTreg differentiation.

Abstract：

:RNA editing of miRNAs, especially in the seed region, adds another layer to miRNA mediated gene regulation which can modify its targets, altering cellular signaling involved in important processes such as differentiation. In this study, we have explored the role of miRNA editing in CD4(+) T cell differentiation. CD4(+) T cells are an integral component of the adaptive immune system. Naïve CD4(+) T cells, on encountering an antigen, get differentiated either into inflammatory subtypes like Th1, Th2 or Th17, or into immunosuppressive subtype Treg, depending on the cytokine milieu. We found C-to-U editing at fifth position of mature miR-100, specifically in Treg. The C-to-U editing of miR-100 is functionally associated with at least one biologically relevant target change, from MTOR to SMAD2. Treg cell polarization by TGFβ1 was reduced by both edited and unedited miR-100 mimics, but percentage of Treg in PBMCs was only reduced by edited miR-100 mimics, suggesting a model in which de-repression of MTOR due to loss of unedited mir-100, promotes tolerogenic signaling, while gain of edited miR-100 represses SMAD2, thereby limiting the Treg. Such delicately counterbalanced systems are a hallmark of immune plasticity and we propose that miR-100 editing is a novel mechanism toward this end.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Negi V,Paul D,Das S,Bajpai P,Singh S,Mukhopadhyay A,Agrawal A,Ghosh B

doi

10.1093/nar/gkv752

subject

Has Abstract

pub_date

2015-09-18 00:00:00

pages

8057-65

issue

16

eissn

0305-1048

issn

1362-4962

pii

gkv752

journal_volume

43

pub_type

杂志文章

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