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An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development

1
Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UK
2
Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK
*
Author to whom correspondence should be addressed.
Epigenomes 2019, 3(1), 7; https://doi.org/10.3390/epigenomes3010007
Received: 29 January 2019 / Revised: 26 February 2019 / Accepted: 5 March 2019 / Published: 13 March 2019
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Abstract

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. View Full-Text
Keywords: micro-RNA; Let-7; mouse genetics micro-RNA; Let-7; mouse genetics
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Koerner, M.V.; Chhatbar, K.; Webb, S.; Cholewa-Waclaw, J.; Selfridge, J.; De Sousa, D.; Skarnes, B.; Rosen, B.; Thomas, M.; Bottomley, J.; Ramirez-Solis, R.; Lelliott, C.; Adams, D.J.; Bird, A. An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development. Epigenomes 2019, 3, 7.

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