An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development
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 f...
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doaj-36c594723aaf41e0a98ad45949e822cf2021-04-02T03:17:02ZengMDPI AGEpigenomes2075-46552019-03-0131710.3390/epigenomes3010007epigenomes3010007An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse DevelopmentMartha V. Koerner0Kashyap Chhatbar1Shaun Webb2Justyna Cholewa-Waclaw3Jim Selfridge4Dina De Sousa5Bill Skarnes6Barry Rosen7Mark Thomas8Joanna Bottomley9Ramiro Ramirez-Solis10Christopher Lelliott11David J. Adams12Adrian Bird13Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UKWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UKWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UKWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UKWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UKWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UKWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKWellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UKWellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, Max Born Crescent, Mayfield Road, Edinburgh EH9 3BF, UKMost 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.http://www.mdpi.com/2075-4655/3/1/7micro-RNALet-7mouse genetics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martha V. Koerner Kashyap Chhatbar Shaun Webb Justyna Cholewa-Waclaw Jim Selfridge Dina De Sousa Bill Skarnes Barry Rosen Mark Thomas Joanna Bottomley Ramiro Ramirez-Solis Christopher Lelliott David J. Adams Adrian Bird |
spellingShingle |
Martha V. Koerner Kashyap Chhatbar Shaun Webb Justyna Cholewa-Waclaw Jim Selfridge Dina De Sousa Bill Skarnes Barry Rosen Mark Thomas Joanna Bottomley Ramiro Ramirez-Solis Christopher Lelliott David J. Adams Adrian Bird An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development Epigenomes micro-RNA Let-7 mouse genetics |
author_facet |
Martha V. Koerner Kashyap Chhatbar Shaun Webb Justyna Cholewa-Waclaw Jim Selfridge Dina De Sousa Bill Skarnes Barry Rosen Mark Thomas Joanna Bottomley Ramiro Ramirez-Solis Christopher Lelliott David J. Adams Adrian Bird |
author_sort |
Martha V. Koerner |
title |
An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development |
title_short |
An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development |
title_full |
An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development |
title_fullStr |
An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development |
title_full_unstemmed |
An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development |
title_sort |
orphan cpg island drives expression of a let-7 mirna precursor with an important role in mouse development |
publisher |
MDPI AG |
series |
Epigenomes |
issn |
2075-4655 |
publishDate |
2019-03-01 |
description |
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. |
topic |
micro-RNA Let-7 mouse genetics |
url |
http://www.mdpi.com/2075-4655/3/1/7 |
work_keys_str_mv |
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