G-patch proteins: important regulators of pre-mRNA splicing and ribosome biogenesis

Pre-mRNA splicing is a fundamental step in eukaryotic gene expression, carried out by the spliceosome. This large and dynamic ribonucleoprotein complex undergoes extensive structural rearrangements during each splicing event. Similarly, ribosome biogenesis is a highly regulated process that requires precise control at every stage, from the transcription of pre-rRNA through its chemical modification and cleavage to the final assembly of mature ribosomal subunits. Central to the regulation of both pre-mRNA splicing and ribosome biogenesis are RNA helicases and their cofactors, notably G-patch proteins. The predominance of G-patch proteins in eukaryotes underscores their evolutionary importance in the increasing complexity of RNA processing and ribosome biogenesis. This review summarizes recent findings on the molecular functions and regulatory roles of various G-patch proteins in the yeasts S. cerevisiae and S. pombe, as well as in humans. Growing evidence indicates that these proteins act as critical cofactors of RNA helicases involved in splicing, facilitating the dynamic transitions required for spliceosome activation, catalysis, and disassembly. Beyond splicing, these proteins also contribute to the regulation of ribosome biogenesis and other aspects of RNA metabolism. Dysregulation or mutation of G-patch proteins have been shown to cause aberrant mRNA maturation, altered splicing patterns, impaired ribosome assembly, and genomic instability. Such perturbations are associated with a range of human diseases, including cancer progression. Despite the essential roles of G-patch proteins in regulating pre-mRNA splicing and ribosome biogenesis, the precise molecular functions and interaction networks of many G-patch proteins remain poorly understood. Future studies aimed at elucidating the mechanisms by which these proteins coordinate RNA processing and ribosome biogenesis are therefore essential. Such investigations may help uncover the molecular basis of G-patch protein-associated diseases and reveal new potential targets for therapeutic intervention.