RPL36A activates ERK pathway and promotes colorectal cancer growth.

Ribosomal protein L36A (RPL36A) was one of the most upregulated proteins in colorectal cancer (CRC), yet its role in colorectal cancer (CRC) remains largely unexplored, with limited studies investigating its expression and biological functions. In this investigation, we confirmed a marked upregulation of RPL36A in CRC tissues, correlating with an adverse prognosis. Silencing RPL36A markedly attenuated CRC cell malignant properties and tumor xenograft growth. Further mechanistic analysis indicated that RPL36A depletion diminished phosphorylated ERK levels, subsequently impacting the expression of c-Myc and ELK1, key downstream effectors in the MAPK/ERK pathway. Notably, the tumor-suppressive effects of RPL36A knockdown could be negated by an ERK activator. Collectively, our findings underscore the oncogenic function of RPL36A in CRC and propose it as a potential target for therapeutic intervention.

Characterization of Recurrent Relevant Genes Reveals a Novel Role of RPL36A in Radioresistant Oral Squamous Cell Carcinoma.

Radioresistance is one of the major factors that contributes to radiotherapy failure in oral cavity squamous cell carcinoma (OSCC). By comparing the prognostic values of 20,502 genes expressed in patients in The Cancer Genome Atlas (TCGA)-OSCC cohort with (n = 162) and without radiotherapy (n = 118), herein identified 297 genes positively correlated with poor disease-free survival in OSCC patients with radiotherapy as the potential radioresistance-associated genes. Among the potential radioresistance-associated genes, 36 genes were upregulated in cancerous tissues relative to normal tissues. The bioinformatics analysis revealed that 60S ribosomal protein L36a (RPL36A) was the most frequently detected gene involved in radioresistance-associated gene-mediated biological pathways. Then, two independent cohorts (n = 162 and n = 136) were assessed to confirm that higher RPL36A transcript levels were significantly associated with a poor prognosis only in OSCC patients with radiotherapy. Mechanistically, we found that knockdown of RPL36A increased radiosensitivity via sensitizing cells to DNA damage and promoted G2/M cell cycle arrest followed by augmenting the irradiation-induced apoptosis pathway in OSCC cells. Taken together, our study supports the use of large-scale genomic data for identifying specific radioresistance-associated genes and suggests a regulatory role for RPL36A in the development of radioresistance in OSCC.

SET7/9 interacts and methylates the ribosomal protein, eL42 and regulates protein synthesis.

Methylation of proteins is emerging to be an important regulator of protein function. SET7/9, a protein lysine methyltransferase, catalyses methylation of several proteins involved in diverse biological processes. SET7/9-mediated methylation often regulates the stability, sub-cellular localization and protein-protein interactions of its substrate proteins. Here, we aimed to identify novel biological processes regulated by SET7/9 by identifying new interaction partners. For this we used yeast two-hybrid screening and identified the large subunit ribosomal protein, eL42 as a potential interactor of SET7/9. We confirmed the SET7/9-eL42 interaction by co-immunoprecipitation and GST pulldown studies. The N-terminal MORN domain of SET7/9 is essential for its interaction with eL42. Importantly, we identified that SET7/9 methylates eL42 at three different lysines - Lys53, Lys80 and Lys100 through site-directed mutagenesis. By puromycin incorporation assay, we find that SET7/9-mediated methylation of eL42 affects global translation. This study identifies a new role of the functionally versatile SET7/9 lysine methyltransferase in the regulation of global protein synthesis.

The sensitivity of the yeast, Saccharomyces cerevisiae, to acetic acid is influenced by DOM34 and RPL36A.

The presence of acetic acid during industrial alcohol fermentation reduces the yield of fermentation by imposing additional stress on the yeast cells. The biology of cellular responses to stress has been a subject of vigorous investigations. Although much has been learned, details of some of these responses remain poorly understood. Members of heat shock chaperone HSP proteins have been linked to acetic acid and heat shock stress responses in yeast. Both acetic acid and heat shock have been identified to trigger different cellular responses including reduction of global protein synthesis and induction of programmed cell death. Yeast HSC82 and HSP82 code for two important heat shock proteins that together account for 1-2% of total cellular proteins. Both proteins have been linked to responses to acetic acid and heat shock. In contrast to the overall rate of protein synthesis which is reduced, the expression of HSC82 and HSP82 is induced in response to acetic acid stress. In the current study we identified two yeast genes DOM34 and RPL36A that are linked to acetic acid and heat shock sensitivity. We investigated the influence of these genes on the expression of HSP proteins. Our observations suggest that Dom34 and RPL36A influence translation in a CAP-independent manner.