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PMID: 24055342 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

The imprinted H19 lncRNA antagonizes let-7 microRNAs.

Molecular cell ·Vol. 52 ·No. 1 ·2013-10-10 ·Pages 101-12

Kallen AN, Zhou XB, Xu J, Qiao C, Ma J, Yan L, Lu L, Liu C, Yi JS, Zhang H, Min W, Bennett AM, Gregory RI, Ding Y, Huang Y

Abstract

Abundantly expressed in fetal tissues and adult muscle, the developmentally regulated H19 long noncoding RNA (lncRNA) has been implicated in human genetic disorders and cancer. However, how H19 acts to regulate gene function has remained enigmatic, despite the recent implication of its encoded miR-675 in limiting placental growth. We noted that vertebrate H19 harbors both canonical and noncanonical binding sites for the let-7 family of microRNAs, which plays important roles in development, cancer, and metabolism. Using H19 knockdown and overexpression, combined with in vivo crosslinking and genome-wide transcriptome analysis, we demonstrate that H19 modulates let-7 availability by acting as a molecular sponge. The physiological significance of this interaction is highlighted in cultures in which H19 depletion causes precocious muscle differentiation, a phenotype recapitulated by let-7 overexpression. Our results reveal an unexpected mode of action of H19 and identify this lncRNA as an important regulator of the major let-7 family of microRNAs.

MeSH Terms
Animals Binding Sites Cell Differentiation Computational Biology Databases, Genetic Gene Expression Profiling/methods Gene Expression Regulation Genomic Imprinting Genotype HEK293 Cells Human Umbilical Vein Endothelial Cells/metabolism Humans Mice MicroRNAs/genetics,metabolism Muscle Development Myoblasts, Skeletal/metabolism Phenotype RNA Interference RNA, Long Noncoding/genetics,metabolism Ribonucleoproteins/metabolism Time Factors Transfection
Chemicals
H19 long non-coding RNA MicroRNAs RNA, Long Noncoding Ribonucleoproteins mirnlet7 microRNA, human mirnlet7 microRNA, mouse
Authors & Affiliations
15 authors, click to expand affiliations / ORCID
Kallen Amanda N
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale Stem Cell Center, Yale University School of Medicine, New Haven, CT 06510, USA.
Zhou Xiao-Bo
Xu Jie
Qiao Chong
Ma Jing
Yan Lei
Lu Lingeng
Liu Chaochun
Yi Jae-Sung
Zhang Haifeng
Min Wang
Bennett Anton M
Gregory Richard I
Ding Ye
Huang Yingqun
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-4164
DOI
10.1016/j.molcel.2013.08.027
Published
2013-10-10
Epub
2013-00-19
Pages
101-12
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC3843377
Subset
IM
Grants
NICHD NIH HHS · K12 HD000849 · United States
NIDDK NIH HHS · P01 DK057751 · United States
NIGMS NIH HHS · GM099811 · United States
NIGMS NIH HHS · R01 GM099801 · United States
NHLBI NIH HHS · R01 HL115148 · United States
NIGMS NIH HHS · GM099801 · United States
NIGMS NIH HHS · R01 GM099811 · United States
NICHD NIH HHS · L50 HD081739 · United States
Databases
GEO
GSE49539
External Links
PubMed source DOI: 10.1016/j.molcel.2013.08.027 PMC Full Text View journal details
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