Conserved Sequences and Secondary RNA Structures Confirm That H19 Functions as a pri-miRNA and as an RNA-binding Protein Platform

The imprinted non-coding RNA H19 was discovered nearly thirty years ago yet, to date, its function has not been ascertained. Recently, H19 has been shown to be the primary transcript of the microRNA miR-675. Both H19 and miR-675 are known to be highly expressed in early fetal development and in an array of solid tumors in humans. We examined H19 sequence and secondary RNA structure in the context of therian evolution to begin to understand the relationship between H19, miR-675, development and oncogenesis. Both H19 sequence and, to a somewhat greater extent, secondary RNA structure is conserved, particularly among eutherians. The pattern of secondary RNA structure conservation in which not only is pre-miR- 675 highly conserved but also a number of other, smaller hairpins and a stable fold, coupled with the presence several conserved poly-pyrimidine tracts that are putative binding sites for the RNA-binding protein IMP1, suggests that H19 has two functions compatible with a non-coding RNA. The first is as pri-miR-675 and the second is as a stable docking platform for a regulatory RNP composed of the 3’ half of the H19 transcript and up to four molecules of IMP1.