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Publication : An Orphan CpG Island Drives Expression of a <i>let-7</i> miRNA Precursor with an Important Role in Mouse Development.

First Author  Koerner MV Year  2019
Journal  Epigenomes Volume  3
Issue  1 Pages  7
PubMed ID  31354981 Mgi Jnum  J:277622
Mgi Id  MGI:6342305 Doi  10.3390/epigenomes3010007
Citation  Koerner MV, et al. (2019) An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development. Epigenomes 3(1):7
abstractText  Most human genes are associated with promoters embedded in non-methylated, G + C-rich CpG islands (CGIs). Not all CGIs are found at annotated promoters, however, raising the possibility that many serve as promoters for transcripts that do not code for proteins. To test this hypothesis, we searched for novel transcripts in embryonic stem cells (ESCs) that originate within orphan CGIs. Among several candidates, we detected a transcript that included three members of the let-7 micro-RNA family: Let-7a-1, let-7f-1, and let-7d. Deletion of the CGI prevented expression of the precursor RNA and depleted the included miRNAs. Mice homozygous for this mutation were sub-viable and showed growth and other defects. The results suggest that despite the identity of their seed sequences, members of the let-7 miRNA family exert distinct functions that cannot be complemented by other members.
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