The imprinted H19 lncRNA antagonizes let-7 microRNAs

Mol Cell. 2013 Oct 10;52(1):101-12. doi: 10.1016/j.molcel.2013.08.027. Epub 2013 Sep 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

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
  • MicroRNAs / metabolism*
  • Muscle Development
  • Myoblasts, Skeletal / metabolism
  • Phenotype
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Ribonucleoproteins / metabolism
  • Time Factors
  • Transfection


  • H19 long non-coding RNA
  • MicroRNAs
  • RNA, Long Noncoding
  • Ribonucleoproteins
  • mirnlet7 microRNA, human
  • mirnlet7 microRNA, mouse

Associated data

  • GEO/GSE49539