5.8S rRNA forms and ribosome heterogeneity in breast cancer.

Abstract

Ribosome heterogeneity can contribute to translation regulation in terms of mRNA selection and translation efficiency. This is particularly true for cancer cells in which oncoribosomes are reported to translate mRNAs encoding for proteins involved in cancer progression. Among other factors, a source of ribosome heterogeneity not yet characterized could be represented by 5.8S rRNA and its three forms distinguished based on their 5' sequence. So far, little is known about the role of the presence of these isoforms in mature ribosomes and how they may contribute to human pathology. Here we investigated the relative abundance of the three 5.8S rRNA isoforms in different contexts. Analyzing total and polysomal RNA from cancer cell lines we detected all the three forms recruited in actively translating ribosomes consistently to the basal levels of their expression. Moreover, we showed that changes in the relative abundance of 5.8S rRNA isoforms can be linked to the process of tumorigenesis in a human HER2 transgenic mouse model which develops spontaneous mammary carcinomas. Finally, from the analysis of breast cancer samples, we observed significant correlations between tumor grade, estrogen receptor status and patient prognosis with the relative abundance of 5.8S rRNA isoforms. These results suggest an additional level of complexity involving 5.8S rRNA and ribosome heterogeneity in cancer pathology.