The Fate of miRNA* Strand through Evolutionary Analysis: Implication for Degradation As Merely Carrier Strand or Potential Regulatory Molecule?

Abstract

BackgroundDuring typical microRNA (miRNA) biogenesis, one strand of a ∼22 nt RNA duplex is preferentially selected for entry into a silencing complex, whereas the other strand, known as the passenger strand or miRNA* strand, is degraded. Recently, some miRNA* sequences were reported as guide miRNAs with abundant expression. Here, we intended to discover evolutionary implication of the fate of miRNA* strand by analyzing miRNA/miRNA* sequences across vertebrates.Principal FindingsMature miRNAs based on gene families were well conserved especially for their seed sequences across vertebrates, while their passenger strands always showed various divergence patterns. The divergence mainly resulted from divergence of different animal species, homologous miRNA genes and multicopy miRNA hairpin precursors. Some miRNA* sequences were phylogenetically conserved in seed and anchor sequences similar to mature miRNAs, while others revealed high levels of nucleotide divergence despite some of their partners were highly conserved. Most of those miRNA precursors that could generate abundant miRNAs from both strands always were well conserved in sequences of miR-#-5p and miR-#-3p, especially for their seed sequences.ConclusionsThe final fate of miRNA* strand, either degraded as merely carrier strand or expressed abundantly as potential functional guide miRNA, may be destined across evolution. Well-conserved miRNA* strands, particularly conservation in seed sequences, maybe afford potential opportunities for contributing to regulation network. The study will broaden our understanding of potential functional miRNA* species.

Investigation of the involvement of MIR185 and its target genes in the development of schizophrenia

“…If this is the case, a plausible hypothesis is that alterations in the mature microRNA sequence could have more dramatic effects, which is also supported by the high conservation of microRNA sequences between species. 57 This hypothesis is consistent with observations from previous studies of microRNA sequences. 58 The present study identified 4 rare variants flanking the premature MIR185 sequence for which a possible regulatory role could not be excluded.…”

MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma

“…S1 and Table S1). This concurrent induction of miR-149* and miR-149 by ER stress is intriguing, as one strand of the miRNA duplex, in particular, miRNA*, resulting from cleavage of premiRNAs by Dicer, is commonly degraded (27). Although how the complementary pair of miR149/149* are both preserved in melanoma cells remains unknown, the unusual occurrence of miR-149*, particularly its increase in response to ER stress, implicates that it may have a functional role in adaptation of melanoma cells to stress conditions.…”

Resveratrol Alters microRNA Expression Profiles in A549 Human Non-Small Cell Lung Cancer Cells

“…The asterisk following the name indicates non-functional miRNA or passenger strand that is released from the miRNA duplex (biologically active miRNA: passenger miRNA) during miRNA biogenesis (O'Toole et al, 2006). Recent studies have suggested that miRNA* affords potential opportunities for contributing to the regulation network (Guo et al, 2010). The microarray we employed contained probes to 723 human miRNAs, including miRNA*.…”