Altered expression and editing of miRNA-100 regulates iTreg differentiation

Negi, V, Paul, D, Das, S, Bajpai, P, Singh, S, Mukhopadhyay, A, Agrawal, A and Ghosh, B 2015, 'Altered expression and editing of miRNA-100 regulates iTreg differentiation' , Nucleic Acids Research .

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Abstract

RNA editing ofmiRNAs, 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. Na¨ıve 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 TGF�1 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.

Item Type: Article
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Journal or Publication Title: Nucleic Acids Research
Publisher: Oxford University Press
ISSN: 0305-1048
Related URLs:
Funders: CSIR, India
Depositing User: A Mukhopadhyay
Date Deposited: 13 Feb 2017 15:11
Last Modified: 09 Aug 2017 06:05
URI: http://usir.salford.ac.uk/id/eprint/41409

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