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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Reprod+Dev
2017 ; 63
(4
): 415-423
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miR-6539 is a novel mediator of somatic cell reprogramming that represses the
translation of Dnmt3b
#MMPMID28603220
Wu F
; Tao L
; Gao S
; Ren L
; Wang Z
; Wang S
; Tian J
; An L
J Reprod Dev
2017[Aug]; 63
(4
): 415-423
PMID28603220
show ga
Global DNA hypomethylation has been shown to be involved in the pluripotency of
induced pluripotent stem (iPS) cells. Relatedly, DNA methyltransferases (DNMTs)
are believed to be a substantial barrier to genome-wide demethylation. There are
two distinct stages of DNMT expression during iPS cell generation. In the earlier
stage of reprogramming, the expression of DNMTs is repressed to overcome
epigenetic barriers. During the late stage, the expression of DNMTs is
upregulated to ensure iPS cells obtain the full pluripotency required for further
development. This fact is strongly reminiscent of microRNAs (miRNAs), critical
regulators of precise gene expression, may be central to coordinate the
expression of DNMTs during reprogramming. Using a secondary inducible system, we
found that miR-6539 had a unique expression dynamic during iPS cell generation
that inversely correlated with DNMT3B protein levels. Enforced upregulation of
miR-6539 during the early stage of reprogramming increased the efficiency of iPS
cell generation, while enforced downregulation impaired efficiency. Further
analysis showed that Dnmt3b mRNA is the likely target of miR-6539. Notably,
miR-6539 repressed Dnmt3b translation via a target site located in the coding
sequence. Our study has therefore identified miR-6539 as a novel mediator of
somatic cell reprogramming and, to the best of our knowledge, is the first to
demonstrate miRNA-mediated translation inhibition in somatic cell reprogramming
via targeting the coding sequence. Our study contributes to understand the
mechanisms that underlie the miRNA-mediated epigenetic remodeling that occurs
during somatic cell reprogramming.