01961nas a2200253   4500008004100000245014300041210006900184260001300253300001100266490000700277520103300284100002601317700002301343700002201366700001601388700001901404700002301423700002201446700002201468700002201490700002301512700001901535856015301554       2015                        eng d00aLet-7 microRNAs target the lineage-specific transcription factor PLZF to regulate terminal NKT cell differentiation and effector function.0 aLet7 microRNAs target the lineagespecific transcription factor P  c2015 May  a517-240 v163 a<p>Lethal-7 (let-7) microRNAs (miRNAs) are the most abundant miRNAs in the genome, but their role in developing thymocytes is unclear. We found that let-7 miRNAs targeted Zbtb16 mRNA, which encodes the lineage-specific transcription factor PLZF, to post-transcriptionally regulate PLZF expression and thereby the effector functions of natural killer T cells (NKT cells). Dynamic upregulation of let-7 miRNAs during the development of NKT thymocytes downregulated PLZF expression and directed their terminal differentiation into interferon-γ (IFN-γ)-producing NKT1 cells. Without upregulation of let-7 miRNAs, NKT thymocytes maintained high PLZF expression and terminally differentiated into interleukin 4 (IL-4)-producing NKT2 cells or IL-17-producing NKT17 cells. Upregulation of let-7 miRNAs in developing NKT thymocytes was signaled by IL-15, vitamin D and retinoic acid. Such targeting of a lineage-specific transcription factor by miRNA represents a previously unknown level of developmental regulation in the thymus.</p>1 aPobezinsky, Leonid, A1 aEtzensperger, Ruth1 aJeurling, Susanna1 aAlag, Amala1 aKadakia, Tejas1 aMcCaughtry, Tom, M1 aKimura, Motoko, Y1 aSharrow, Susan, O1 aGuinter, Terry, I1 aFeigenbaum, Lionel1 aSinger, Alfred  uhttps://www.umass.edu/veterinary-animal-sciences/research-faculty/publications/let-7-micrornas-target-the-lineage-specific-transcription-factor-plzf