Predicting human RNA quadruplex helicases through comparative sequence approaches and helicase mRNA interactome analyses

Biochem Cell Biol. 2021 Feb 15. doi: 10.1139/bcb-2020-0590. Online ahead of print.ABSTRACTRNA quadruplexes are non-canonical nucleic acid structures involved in several human disease states and are regulated by a specific subset of RNA helicases. Given the difficulty in identifying RNA quadruplex helicases due to the multifunctionality of these enzymes, we sought to provide a comprehensive in silico analysis of features found in validated RNA quadruplex helicases to predict novel human RNA quadruplex helicases. Using the 64 human RNA helicases, we correlated their amino acid compositions with subsets of RNA quadruplex helicases categorized by varying level of evidence of RNA quadruplex interaction. Utilizing phylogenetic and synonymous/non-synonymous substitution analyses, we identified an evolutionarily conserved pattern involving predicted intrinsic disorder and a previously identified motif. We analyzed available next generation sequencing data to determine which RNA helicases were directly interacting with predicted RNA quadruplex regions intracellularly and elucidated a relationship with miRNA binding sites adjacent to RNA quadruplexes. Finally, we employed a phylogenetic analysis of all 64 human RNA helicases to establish how RNA quadruplex detection and unwinding activity may be conserved among helicase subfamilies. This work furthers understanding of commonalities between RNA quadruplex helicases and provides support for the future validation of several human RNA heli...
Source: Biochemistry and Cell Biology - Category: Biochemistry Authors: Source Type: research