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Teleost fishes share a duplication of their entire genomes. We report here on a computational survey of structured non-coding RNAs (ncRNAs) in teleost genomes, focusing on the fate of fish-specific duplicates. As in other metazoan groups, we find evidence of a large number (11,543) of structured RNAs, most of which (~86%) are clade-specific or evolve so fast that their tetrapod homologs cannot be detected. In surprising contrast to protein-coding genes, the fish-specific genome duplication did not lead to a large number of paralogous ncRNAs: only 188 candidates, mostly microRNAs, appear in a larger copy number in teleosts than in tetrapods, suggesting that large-scale gene duplications do not play a major role in the expansion of the vertebrate ncRNA inventory.

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.

An entirely new area of pharmacology is developing from an understanding of endogenous functional long noncoding RNAs (lncRNAs). Potential treatment options for cancer, diabetes and HIV are derived from findings that specific lncRNAs, which regulate networks of genes, can be targeted to treat the disorders. Emerging evidence indicates that specific lncRNAs also contribute to autism spectrum disorder (ASD) risk. Here, we review this evidence and explore possible treatment advances for ASD based on inhibitory RNA-based therapies.