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PMID: 22684254 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r.

Nature cell biology ·Vol. 14 ·No. 7 ·2012-06-10 ·Pages 659-65

Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L, Smits G, Reik W

Abstract

The H19 large intergenic non-coding RNA (lincRNA) is one of the most highly abundant and conserved transcripts in mammalian development, being expressed in both embryonic and extra-embryonic cell lineages, yet its physiological function is unknown. Here we show that miR-675, a microRNA (miRNA) embedded in H19's first exon, is expressed exclusively in the placenta from the gestational time point when placental growth normally ceases, and placentas that lack H19 continue to grow. Overexpression of miR-675 in a range of embryonic and extra-embryonic cell lines results in their reduced proliferation; targets of the miRNA are upregulated in the H19 null placenta, including the growth-promoting insulin-like growth factor 1 receptor (Igf1r) gene. Moreover, the excision of miR-675 from H19 is dynamically regulated by the stress-response RNA-binding protein HuR. These results suggest that H19's main physiological role is in limiting growth of the placenta before birth, by regulated processing of miR-675. The controlled release of miR-675 from H19 may also allow rapid inhibition of cell proliferation in response to cellular stress or oncogenic signals.

MeSH Terms
Animals Cell Line Cell Proliferation DEAD-box RNA Helicases/metabolism Down-Regulation ELAV Proteins/genetics,metabolism Exons Female Gene Expression Regulation, Developmental Gestational Age Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Knockout Mice, Transgenic MicroRNAs/metabolism Placenta/metabolism Placentation Pregnancy RNA Interference RNA, Long Noncoding RNA, Untranslated/metabolism Receptor, IGF Type 1/genetics,metabolism Ribonuclease III/metabolism Signal Transduction Time Factors Transfection
Chemicals
ELAV Proteins H19 long non-coding RNA MIRN675 microRNA, mouse MicroRNAs RNA, Long Noncoding RNA, Untranslated Receptor, IGF Type 1 Dicer1 protein, mouse Drosha protein, mouse Ribonuclease III DEAD-box RNA Helicases
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Keniry Andrew
Epigenetics Programme, Babraham Institute, Cambridge, CB22 3AT, UK.
Oxley David
Monnier Paul
Kyba Michael
Dandolo Luisa
Smits Guillaume
Reik Wolf
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2521
Published
2012-06-10
Epub
2012-00-10
Pages
659-65
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3389517
Subset
IM
Grants
Wellcome Trust · 095645 · United Kingdom
NHLBI NIH HHS · U01HL100407 · United States
Biotechnology and Biological Sciences Research Council · BB/H008071/1 · United Kingdom
Medical Research Council · G0801156 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBS/E/B/0000S119 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBS/E/B/0000C214 · United Kingdom
Biotechnology and Biological Sciences Research Council · BBS/E/B/0000H109 · United Kingdom
Medical Research Council · G0801156(87767) · United Kingdom
NHLBI NIH HHS · U01 HL100407 · United States
External Links
PubMed source DOI: 10.1038/ncb2521 PMC Full Text View journal details
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