Evolutionary conservation supports ancient origin for Nudt16, a nuclear-localized, RNA-binding, RNA-decapping enzyme

Area of Science:

• Molecular Biology
• Evolutionary Biology
• Biochemistry

Background:

• Nudt16p is a nuclear RNA decapping enzyme identified in Xenopus and mammals.
• RNA decapping is crucial for regulating gene expression and mRNA turnover.

Purpose of the Study:

• To investigate the evolutionary conservation and functional divergence of Nudt16p and its paralogs across metazoans.
• To characterize the RNA binding and decapping activities of Nudt16p orthologs and the related Syndesmos protein.

Main Methods:

• Bioinformatic analysis to identify Nudt16p orthologs and paralogs in diverse species.
• In vitro biochemical assays to assess RNA binding and decapping activity of insect Nudt16p.
• Structural and functional analysis of Syndesmos in tetrapods.

Main Results:

• Putative Nudt16p orthologs were identified in 57 organisms, from humans to Cnidaria.
• Insect Nudt16p demonstrated conserved RNA binding and m(7)G cap hydrolysis activity.
• A paralog, Syndesmos, arose in tetrapods via gene duplication, retaining RNA binding but losing decapping function.
• Syndesmos localizes to the cytoplasmic membrane in tetrapods, unlike nuclear Nudt16p.

Conclusions:

• The ancient Nudt16 protein and its nuclear RNA decapping function are conserved throughout metazoan evolution.
• Gene duplication led to the emergence of Syndesmos, a functionally divergent paralog involved in cytoplasmic processes.
• This study underscores the evolutionary persistence of nuclear RNA degradation pathways.