Structural modularity of microRNA precursors

Miler Lee, University of Pennsylvania

An RNA molecule is made up of a linear sequence of nucleotides, which form pairwise interactions that define its folded three-dimensional structure. For smaller RNAs, the folded configuration reflects a globally minimal free energy state, such that changing the nucleotide sequence or adding additional sequence might significantly alter the minimum free energy structure. Previously we showed that a class of non-protein-coding RNAs, microRNAs, exhibit the property of structural self containment – given any arbitrary genomic sequence context, the precursor miRNA hairpin structure will tend to maintain a robust substructure; this is a property that distinguishes pre-miRNAs from most other classes of non-coding RNAs. Here, we propose that miRNAs’ trend toward high self containment reflects their modular origins – i.e., the pre-miRNA may constitute a modular unit, remaining structurally robust throughout an evolutionary history characterized by rapid duplication, rearrangement, and sequence change.

Abstract Author(s): Miler T. Lee and Junhyong Kim