Impact of RRP1B Variants on the Phenotype, Progression, and Metastasis of Cervical Cancer.

Metastasis is a key determinant of cancer progression, influenced significantly by genetic mechanisms. RRP1B, primarily a nucleolar protein, emerges as a suppressor of metastasis, forming alliances with various cellular components and modulating gene expression. This study investigates the involvement of the ribosomal RNA processing 1 homolog B (RRP1B) gene in metastasis regulation in cervical cancer. Through a comprehensive analysis of 172 cervical cancer patients, we evaluated five RRP1B single nucleotide polymorphisms (SNPs) (rs2838342, rs7276633, rs2051407, rs9306160, and rs762400) for their associations with clinicopathological features and survival outcomes. Significant associations were observed between specific genetic variants and clinicopathological parameters. Notably, the A allele of rs2838342 was associated with reduced odds of advanced tumor size, worse prognosis, and, preliminarily, distant metastasis, while the T allele of rs7276633 correlated with a decreased risk of higher tumor size and worse prognosis. Additionally, the C allele of rs2051407 demonstrated protective effects against larger tumors, metastasis, and adverse prognosis. The rs9306160 C allele exhibited a protective effect against metastasis. The rs762400 G allele was significant for reduced tumor size and metastasis risk. Furthermore, the rs2838342 A allele, rs7276633 T allele, rs2051407 C allele, and rs762400 G allele were associated with improved overall survival, demonstrating their potential significance in predicting prognoses in cervical cancer. Linkage disequilibrium and haplotypes analysis enabled us to evaluate the collective effect of the analyzed SNPs, which was in line with the results of allelic models. Our findings underscore the clinical relevance of RRP1B SNPs as prognostic markers in cervical cancer, shedding light on the intricate interplay between genetic factors and disease-progression dynamics. This research provides critical insights for future investigations and underscores the importance of incorporating RRP1B SNP detection into prognostic-assessment tools for accurate prediction of disease outcomes in cervical cancer.

The ribosomal RNA processing 1B:protein phosphatase 1 holoenzyme reveals non-canonical PP1 interaction motifs.

The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of substrates by associating with >200 regulatory proteins to form specific holoenzymes. The major PP1 targeting protein in the nucleolus is RRP1B (ribosomal RNA processing 1B). In addition to selectively recruiting PP1ß/PP1γ to the nucleolus, RRP1B also has a key role in ribosome biogenesis, among other functions. How RRP1B binds PP1 and regulates nucleolar phosphorylation signaling is not yet known. Here, we show that RRP1B recruits PP1 via established (RVxF/SILK/ΦΦ) and non-canonical motifs. These atypical interaction sites, the PP1ß/γ specificity, and N-terminal AF-binding pockets rely on hydrophobic interactions that contribute to binding and, via phosphorylation, regulate complex formation. This work advances our understanding of PP1 isoform selectivity, reveals key roles of N-terminal PP1 residues in regulator binding, and suggests that additional PP1 interaction sites have yet to be identified, all of which are necessary for a systems biology understanding of PP1 function.