RNA Polymerase Subunits and Ribosomal Proteins: An Overview and Their Genetic Impact on Complex Human Traits.

Abstract

Accurate gene expression is fundamental for sustaining life, enabling adaptive responses to routine tasks and management of urgent cellular environments. RNA polymerases (RNAP I, RNAP II, and RNAP III) and ribosomal proteins (RPs) play pivotal roles in the precise synthesis of proteins from DNA sequences. In this review, we briefly examined the structure and function of their constituent proteins and explored to characterize these proteins and the genes encoding them, particularly in terms of their expression quantitative trait loci (eQTL) associated with complex human traits. We gathered a comprehensive set of 4007 genome-wide association study (GWAS) signal-eQTL pairs, aligning GWAS Catalog signals with eQTLs across various tissues for the genes involved. These pairs spanned 16 experimental factor ontology (EFO) parent terms defined in European Bioinformatics Institute (EBI). A substantial majority (83.4%) of the pairs were attributed to the genes encoding RPs, especially RPS26 (32.9%). This large proportion was consistent across all tissues (15.5~81.9%), underscoring its extensive impact on complex human traits. Notably, these proportions of EFO terms differed significantly (p < 0.0031) from those for RNAPs. Brain-specific pairs for POLR3H, a component of RNAP III, were implicated in neurological disorders. The largest number of pairs in RNAP I was found for POLR1H, encoding RPA12, a built-in transcription factor essential for high transcriptional efficiency of RNAP I. RNAP II-related pairs were less abundant, with unique structural organization featuring minimal subunits for flexible transcription of a diverse range of genes with customized dissociable subunits. For instance, RPB4 encoded by POLR2D, the RNAP II gene with the most pairs, forms its dissociable stalk module with RPB7. This study provides insightful genetic characteristics of RPs and RNAPs, with a priority emphasis on RPS26, POLR1H, POLR2D, and POLR3H, for future studies on the impact of individual genetic variation on complex human traits.