title: 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.
authors.affiliation: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Vinny
authors.initials: V
authors.lastname: Negi
authors.affiliation: Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Deepanjan
authors.initials: D
authors.lastname: Paul
authors.affiliation: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Das
authors.affiliation: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Bajpai
authors.affiliation: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Suchita
authors.initials: S
authors.lastname: Singh
authors.affiliation: Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India Genomics & Molecular Medicine, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Arijit
authors.initials: A
authors.lastname: Mukhopadhyay
authors.affiliation: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Agrawal
authors.affiliation: Molecular Immunogenetics Laboratory and Centre of Excellence for Translational Research in Asthma & Lung disease, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India Academy of Scientific & Innovative Research, CSIR-Institute of Genomics and Integrative Biology, Delhi 110007, India bghosh@igib.res.in.
authors.forename: Balaram
authors.initials: B
authors.lastname: Ghosh
mesh_terms: D020413:3' Untranslated Regions; D015496:CD4-Positive T-Lymphocytes / Q000145:classification; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D017393:RNA Editing; D051899:Smad2 Protein / Q000235:genetics; D016176:T-Lymphocyte Subsets; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; C544266:MIRN100 microRNA, human; D035683:MicroRNAs; D051899:Smad2 Protein; D058570:TOR Serine-Threonine Kinases