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

Martha Koerner, Kashyap Chhatbar, Shaun Webb, Justyna Cholewa-Waclaw, Jim Selfridge, Dina De Sousa, Bill Skarnes, Barry Rosen, Mark Thomas, Joanna Bottomley, Ramiro Ramires-Solis, Christopher Lelliott, David Adams, Adrian Bird

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Number of pages14
Issue number1
Publication statusPublished - 13 Mar 2019


  • micro-RNA
  • Let-7
  • mouse genetics

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