Altered expression and editing of miRNA-100 regulates iTreg differentiation

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

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 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.

Citation

Negi, V., Paul, D., Das, S., Bajpai, P., Singh, S., Mukhopadhyay, A., …Ghosh, B. (2015). Altered expression and editing of miRNA-100 regulates iTreg differentiation. Nucleic Acids Research, 43(16), 8057-8065. https://doi.org/10.1093/nar/gkv752

• Journal Article Type: Article
• Acceptance Date: Jul 14, 2015
• Publication Date: Jul 23, 2015
• Deposit Date: Feb 13, 2017
• Publicly Available Date: Feb 13, 2017
• Journal: Nucleic Acids Research
• Print ISSN: 0305-1048
• Electronic ISSN: 1362-4962
• Publisher: Oxford University Press
• Volume: 43
• Issue: 16
• Pages: 8057-8065
• DOI: https://doi.org/10.1093/nar/gkv752
• Publisher URL: http://dx.doi.org/10.1093/nar/gkv752
• Related Public URLs: https://academic.oup.com/nar