The Protein Network Essential for Ribosome Biogenesis Organized by the Multifunctional Rrp5 Protein (A Review)

The production of ribosomes occurs through a complex pathway that requires the precise cleavage of pre-rRNA to generate four mature precursor rRNA components of the two ribosomal subunits. This highly regulated process involves numerous assembly factors, including RNA-binding proteins. Rrp5 is one of very few known RNA-binding proteins that is essential for the assembly of both the small and large subunits in eukaryotic organisms. Rrp5 harbors multiple S1 domains in tandem, which bind both RNA and proteins, followed by tandem Tetratrico Peptide Repeat domains that bind proteins. Notably, Rrp5 lacks a direct RNA cleaving ability, and thus must collaborate with other protein modules to carry out pre-rRNA cleavage events. Despite being a central player in ribosome biogenesis, the precise functions of Rrp5 remain poorly defined, particularly in complex organisms. In this review, we summarize the architecture of Rrp5, its confirmed and potential partners, and discuss the potential mechanisms for its multiple functions. A better understanding of the role and regulation of Rrp5 in development might enhance our understanding of a class of human diseases called ribosomopathies, where malfunctions in specific tissues are associated with defective ribosomal functions.