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

doi:10.3390/epigenomes3010007

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 journal › Article › peer-review

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.

Original language	English
Number of pages	14
Journal	Epigenomes
Volume	3
Issue number	1
DOIs	https://doi.org/10.3390/epigenomes3010007
Publication status	Published - 13 Mar 2019

Keywords / Materials (for Non-textual outputs)

micro-RNA
Let-7
mouse genetics

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10.3390/epigenomes3010007

An Orphan CpG PUB OA CC BY epigenomes-03-00007
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0). (http://creativecommons.org/licenses/by/4.0/).
Final published version, 1.68 MBLicence: Creative Commons: Attribution (CC-BY)

https://www.mdpi.com/2075-4655/3/1/7

Towards understanding and treatment of MeCP2-related disorders
Bird, A. (Principal Investigator)
UK-based charities
1/01/16 → 30/06/22
Project: Research

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Koerner, M., Chhatbar, K., Webb, S., Cholewa-Waclaw, J., Selfridge, J., De Sousa, D., Skarnes, B., Rosen, B., Thomas, M., Bottomley, J., Ramires-Solis, R., Lelliott, C., Adams, D., & Bird, A. (2019). An Orphan CpG Island Drives Expression of a let-7 miRNA Precursor with an Important Role in Mouse Development. Epigenomes, 3(1). https://doi.org/10.3390/epigenomes3010007

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

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.",

keywords = "micro-RNA, Let-7, mouse genetics",

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

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AU - Koerner, Martha

AU - Chhatbar, Kashyap

AU - Webb, Shaun

AU - Cholewa-Waclaw, Justyna

AU - Selfridge, Jim

AU - De Sousa, Dina

AU - Skarnes, Bill

AU - Rosen, Barry

AU - Thomas, Mark

AU - Bottomley, Joanna

AU - Ramires-Solis, Ramiro

AU - Lelliott, Christopher

AU - Adams, David

AU - Bird, Adrian

N1 - (This article belongs to the Special Issue A Commemorative Issue in Honor of Professor Denise P. Barlow: Genomic Imprinting, Epigenetics and Transcriptional Control)

PY - 2019/3/13

Y1 - 2019/3/13

N2 - 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.

AB - 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.

KW - micro-RNA

KW - Let-7

KW - mouse genetics

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DO - 10.3390/epigenomes3010007

M3 - Article

SN - 2075-4655

VL - 3

JO - Epigenomes

JF - Epigenomes

IS - 1

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

Towards understanding and treatment of MeCP2-related disorders

Cite this