Fibrillarin regulates oncogenic protein pools and ribosome protein composition in triple-negative breast cancer

Cancer cells hijack various gene expression regulation programs to support their increased metabolic demands, including translation. Emerging data suggests that specific aspects of translation, such as initiation, fidelity and efficiency, can be regulated by alterations in any of the ribosome components, being ribosomal proteins or RNA (rRNA). rRNA is highly decorated with chemical modifications that can influence its stability, folding, and interaction with other molecules. Thus, we hypothesised that chemical modifications may play an essential role in controlling the pool of oncogenic proteins in triple-negative breast cancer (TNBC). As a result, this study focuses on studying the role of fibrillarin, the catalytic enzyme responsible for the deposition of 2'-O-methylation, the most abundant rRNA modification, in the context of TNBC’s aetiology and tumour progression. Using Ribosome profiling (Ribo-seq), we identified proto-oncogenes, e.g., MTA1, IRAK1 and TMSB10, whose translation efficiency is downregulated upon fibrillarin depletion. Understanding the dynamics between 2'-O-methylation and translational control of gene expression of these proto-oncogenes will facilitate the development of effective cures against TNBC.