Unraveling Ribosome Heterogeneity: Implications for Metastasis and Beyond

Introduction

Protein translation, considered a mere reflection of transcription, emerges as a regulatory hub, shaping proteomes and directing cellular outcomes. This is due to the existence of heterogeneous ribosome populations, yielding specialized ribosomes that drive context-dependent translation.

Technological Advances

While technological advances enable mapping of ribosomal diversity, questions remain as to the prevalence of the phenomenon and the mechanisms by which specialized ribosomes confer specific functions. Studies propose the presence of onco-ribosomes promoting oncogenic translational programs and regulating disease-related functions.

Metastasis and Gene Expression

Metastasis, the deadly spread of cancer cells to remote organs, is a key process that relies on the rewiring of gene expression networks. Accordingly, our work shows that changes in the expression of coding and non-coding genes affect metastatic potential and correlate with patient prognosis.

RNA Modifications and Ribosomal Heterogeneity

We further show that environmentally-regulated RNA modifications add to ribosomal heterogeneity. Yet, the involvement of specialized ribosomes in metastasis development is mostly unknown.

Research Proposal

Here, I propose to map ribosomal heterogeneity in metastatic cancers and decipher the 'ribosomal code' empowering specialized ribosomes to promote oncogenic translational programs and drive metastasis.

Methodology

Using cell lines, animal models, and patient-derived samples, we will:

1. Chart metastatic patterns of rRNA and ribosomal proteins (RPs).
2. Investigate snoRNAs and rRNA modifications they guide.
3. Employ in vivo and in vitro assays to uncover individual RPs and snoRNAs influencing ribosomal functions and metastasis formation.
4. Investigate their mechanisms of action.

Potential Impact

These genes and their metastatic patterns, along with metastasis-specific rRNA compositions, may serve as cancer biomarkers and targets for therapy. This research will advance our understanding of molecular mechanisms underlying ribosome heterogeneity and elucidate the involvement of specialized ribosomes in cancer progression.