Analysis of Structural Strand Asymmetry in Non-coding RNAs

Many RNA functions are determined by their specific secondary and tertiary structures. These structures are folded by the canonical G::C and A::U base pairings as well as by the non-canonical G::U complementary bases. G::U base pairings in RNA secondary structures may induce structural asymmetries between the transcribed and non-transcribed strands in their corresponding DNA sequences. This is likely so because the corresponding C::A nucleotides of the complementary strand do not pair. As a consequence, the secondary structures that form from a genomic sequence depend on the strand transcribed. We explore this idea to investigate the size and significance of both global and local secondary structure formation differentials in several non-coding RNA families and mRNAs. We show that both thermodynamic stability of global RNA structures in the transcribed strand and RNA structure strand asymmetry are statistically stronger than that in randomized versions preserving the same di-nucleotide base composition and length, and is especially pronounced in microRNA precursors. We further show that a measure of local structural strand asymmetry within a fixed window size, as could be used in detecting and characterizing transcribed regions in a full genome scan, can be used to predict the transcribed strand across ncRNA families.