Abstract

All multicellular organisms studied to date have three right open reading frame kinase genes (designated riok-1, riok-2 and riok-3). Current evidence indicates that riok-1 and riok-2 have essential roles in ribosome biosynthesis, and that the riok-3 gene assists this process. In the present study, we conducted a detailed bioinformatic analysis of the riok gene family in 25 parasitic flatworms (platyhelminths) for which extensive genomic and transcriptomic data sets are available. We found that none of the flatworms studied have a riok-3 gene, which is unprecedented for multicellular organisms. We propose that, unlike in other eukaryotes, the loss of RIOK-3 from flatworms does not result in an evolutionary disadvantage due to the unique biology and physiology of this phylum. We show that the loss of RIOK-3 coincides with a loss of particular proteins associated with essential cellular pathways linked to cell growth and apoptosis. These findings indicate multiple, key regulatory functions of RIOK-3 in other metazoan species. Taking advantage of a known partial crystal structure of human RIOK-1, molecular modelling revealed variability in nucleotide binding sites between flatworm and human RIOK proteins.

Highlights

  • All multicellular organisms studied to date have three right open reading frame kinase genes

  • We found that none of the flatworms studied have a riok[3] gene, which is unprecedented for multicellular organisms

  • We show that the loss of RIOK-3 coincides with a loss of particular proteins associated with essential cellular pathways linked to cell growth and apoptosis

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Summary

Introduction

All multicellular organisms studied to date have three right open reading frame kinase genes (designated riok-1, riok-2 and riok-3). We have curated the riok gene family for 12 parasitic roundworms (nematodes), predicted functional domains of parasite RIOK proteins using three-dimensional (3D) structural modelling, and prioritized existing kinase inhibitors for repurposing against RIOK-1 of parasitic nematodes[15,16]. Extending these studies[15,16], we conducted a detailed investigation of the riok gene family in socioeconomically important parasitic flatworms.

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