Selective microRNA-Offset RNA expression in human embryonic stem cells

PLoS One. 2015 Mar 30;10(3):e0116668. doi: 10.1371/journal.pone.0116668. eCollection 2015.


Small RNA molecules, including microRNAs (miRNAs), play critical roles in regulating pluripotency, proliferation and differentiation of embryonic stem cells. miRNA-offset RNAs (moRNAs) are similar in length to miRNAs, align to miRNA precursor (pre-miRNA) loci and are therefore believed to derive from processing of the pre-miRNA hairpin sequence. Recent next generation sequencing (NGS) studies have reported the presence of moRNAs in human neurons and cancer cells and in several tissues in mouse, including pluripotent stem cells. In order to gain additional knowledge about human moRNAs and their putative development-related expression, we applied NGS of small RNAs in human embryonic stem cells (hESCs) and fibroblasts. We found that certain moRNA isoforms are notably expressed in hESCs from loci coding for stem cell-selective or cancer-related miRNA clusters. In contrast, we observed only sparse moRNAs in fibroblasts. Consistent with earlier findings, most of the observed moRNAs derived from conserved loci and their expression did not appear to correlate with the expression of the adjacent miRNAs. We provide here the first report of moRNAs in hESCs, and their expression profile in comparison to fibroblasts. Moreover, we expand the repertoire of hESC miRNAs. These findings provide an expansion on the known repertoire of small non-coding RNA contents in hESCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line
  • Computational Biology
  • Gene Expression Profiling
  • Gene Expression*
  • Gene Library
  • High-Throughput Nucleotide Sequencing
  • Human Embryonic Stem Cells / metabolism*
  • Humans
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Molecular Sequence Annotation
  • Molecular Sequence Data
  • RNA, Small Untranslated / chemistry
  • RNA, Small Untranslated / genetics*
  • Sequence Alignment


  • MicroRNAs
  • RNA, Small Untranslated

Grant support

This study was supported by Academy of Finland, SA GW TO (; Biocenter Finland, LH (; Sigrid Juselius Foundation, SA TO (; Swedish Research Council, OH ( The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.