Abstract
BackgroundPrevious studies have shown that microRNA precursors (pre-miRNAs) have considerably more stable secondary structures than other native RNAs (tRNA, rRNA, and mRNA) and artificial RNA sequences. However, pre-miRNAs with ultra stable secondary structures have not been investigated. It is not known if there is a tendency in pre-miRNA sequences towards or against ultra stable structures? Furthermore, the relationship between the structural thermodynamic stability of pre-miRNA and their evolution remains unclear.ResultsWe investigated the correlation between pre-miRNA sequence conservation and structural stability as measured by adjusted minimum folding free energies in pre-miRNAs isolated from human, mouse, and chicken. The analysis revealed that conserved and non-conserved pre-miRNA sequences had structures with similar average stabilities. However, the relatively ultra stable and unstable pre-miRNAs were more likely to be non-conserved than pre-miRNAs with moderate stability. Non-conserved pre-miRNAs had more G+C than A+U nucleotides, while conserved pre-miRNAs contained more A+U nucleotides. Notably, the U content of conserved pre-miRNAs was especially higher than that of non-conserved pre-miRNAs. Further investigations showed that conserved and non-conserved pre-miRNAs exhibited different structural element features, even though they had comparable levels of stability.ConclusionsWe proposed that there is a correlation between structural thermodynamic stability and sequence conservation for pre-miRNAs from human, mouse, and chicken genomes. Our analyses suggested that pre-miRNAs with relatively ultra stable or unstable structures were less favoured by natural selection than those with moderately stable structures. Comparison of nucleotide compositions between non-conserved and conserved pre-miRNAs indicated the importance of U nucleotides in the pre-miRNA evolutionary process. Several characteristic structural elements were also detected in conserved pre-miRNAs.
Highlights
IntroductionPrevious studies have shown that microRNA precursors (pre-miRNAs) have considerably more stable secondary structures than other native RNAs (tRNA, rRNA, and mRNA) and artificial RNA sequences
Previous studies have shown that microRNA precursors have considerably more stable secondary structures than other native RNAs and artificial RNA sequences
Potential artefacts arising from difference sequence lengths were excluded by using adjusted MFEs (AMFEs) for comparisons
Summary
Previous studies have shown that microRNA precursors (pre-miRNAs) have considerably more stable secondary structures than other native RNAs (tRNA, rRNA, and mRNA) and artificial RNA sequences. MicroRNAs (miRNAs) are small endogenous non-coding RNAs that regulate expression at the post-transcriptional level in animals and plants [1]. Both plant and animal miRNAs are cleaved from one arm of foldback precursors (pre-miRNAs). The human nuclear processing enzyme Drosha has been found to selectively cleave pre-miRNAs hairpins bearing a large terminal loop (≥ 10 nucleotides) [18]. This type of terminal loop could result in pre-miRNA instability. The question remains: is there a tendency against ultra stable secondary structures in pre-miRNA sequences?
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