Pre-rRNA spatial distribution and functional organization of the nucleolus

Area of Science:

• Cell Biology
• Molecular Biology
• Evolutionary Biology

Background:

• The nucleolus is central to ribosome biogenesis, involving complex processing of ribosomal RNA (rRNA) precursors.
• The precise spatial organization of these processing steps within nucleolar substructures and their adaptation to cellular needs are not fully understood.

Purpose of the Study:

• To investigate the spatiotemporal dynamics of ribosomal subunit precursor (pre-rRNA) processing within human nucleolar compartments.
• To elucidate the relationship between pre-rRNA processing, nucleolar architecture, and cellular proliferation.
• To explore the evolutionary implications of nucleolar structure on ribosome biogenesis efficiency.

Main Methods:

• Spatiotemporal analysis of pre-rRNA processing in human nucleoli.
• Investigating the impact of 5' external transcribed spacer (5' ETS) processing perturbations.
• Comparative analysis of nucleolar structures in amniotes and anamniotes.

Main Results:

• Small subunit (SSU) processomes are localized in fibrillar centre (FC)-dense fibrillar component (DFC)-periphery dense fibrillar component (PDFC) domains, while large subunit (LSU) pre-rRNAs transit to PDFC-granular component regions.
• Slowly proliferating cells show impaired 5' ETS-centered SSU processing, associated with FC-DFC unit remodeling and reduced SSU precursor export.
• Anamniote bipartite nucleoli exhibit distinct 5' ETS distribution and slower pre-rRNA flux compared to amniote multilayered nucleoli.
• Introducing a FC/DFC interface to bipartite nucleoli improved processing efficiency.

Conclusions:

• 5' ETS-centered processing is crucial for maintaining nucleolar substructures and efficient SSU biogenesis.
• Nucleolar architecture, particularly the nested FC-DFC units in amniotes, is optimized for pre-rRNA processing.
• Evolutionary divergence in nucleolar structure correlates with differences in ribosome biogenesis efficiency.