A working model for cytoplasmic assembly of H/ACA snoRNPs

Pseudouridylation occurs on all types of cellular RNAs. As a catalytic component of nuclear H/ACA ribonucleoproteins (RNPs), the pseudouridine synthase dyskerin exerts a general impact on multiple fundamental cellular processes. Although this protein has been investigated in detail, its cytoplasmic roles have been largely overlooked, despite the identification of a minor splice variant showing a prevalent cytoplasmic localization. In this perspective, we discuss the role of this minor isoform in the composition, assembly, and function of H/ACA RNPs. On this basis, we propose a model in which cytoplasmic regulation modulates the integration of distinct dyskerin isoforms within preassembly complexes, consequently also influencing their nuclear import. This mechanism could govern pseudouridylation, cellular growth, and mRNA translation. Impact statement Human Dyskerin is the pseudouridine-synthase component of H/ACA RNPs. Two isoforms have been characterized: the abundant Iso1, mainly nuclear, and Iso3, mainly cytoplasmic but occasionally imported into nuclei. We propose a model accounting for a regulated participation of both isoforms in the cytoplasmic pre-assembly of H/ACA RNPs.