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.
A team led by researchers at Yale University School of Medicine demonstrate that H19 modulates let-7 availability by acting as a molecular sponge using H19 knockdown and overexpression, combined with in vivo crosslinking and genome-wide transcriptome analysis. 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. Their 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.
- Kallen AN et al. (2013) The Imprinted H19 LncRNA Antagonizes Let-7 MicroRNAs. Molecular Cell [Epub ahead of print]. [abstract]