Computational prediction of nonenzymatic RNA degradation patterns

Abstract

Since the beginning of XXI century, the increasing interest in the research of ribonucleic acids has been observed in response to a surprising discovery of the role that RNA molecules play in the biological systems. It was demonstrated that they do not only take part in the protein synthesis (mRNA, rRNA, tRNA) but also are involved in the regulation of gene expression. Several classes of small regulatory RNAs have been discovered (e.g. microRNA, small interfering RNA, piwiRNA). Most of them are excised from specific double-stranded RNA precursors by enzymes that belong to the RNaseIII family (Drosha, Dicer or Dicer-like proteins). More recently, it has been shown that small regulatory RNAs are also generated as stable intermediates of RNA degradation (so called RNA fragments originating from tRNA, snRNA, snoRNA etc.). Unfortunately, the mechanisms underlying biogenesis of the RNA fragments remain unclear. It is thought that several factors may be involved in the formation of the RNA fragments. The most important are specific RNases, RNA-protein interactions and RNA structure.  

In this work, we focus on RNA primary and secondary structures as factors influencing RNA stability and consequently the pattern of RNA fragmentation. Earlier, we identified major structural factors affecting non-enzymatic RNA degradation. Now based on these data we developed a new branch-and-cut algorithm that is able to predict the products of large RNA molecules hydrolysis in vitro. We also present the experimental data that verify the results generated using this algorithm.