Regulators of rDNA array morphology in fission yeast

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Nucleolar morphology is a key indicator of ribosome biogenesis.
• Regulation of ribosomal DNA (rDNA) morphology is crucial for ribosome production but understudied.
• rDNA gene transcription significantly impacts ribosome output.

Purpose of the Study:

• To investigate the relationship between rDNA array morphology and ribosome biogenesis activity.
• To establish a live visual marker for quantitative analysis of rDNA organization.
• To identify genetic factors influencing rDNA morphology and ribosome production.

Main Methods:

• Development of GapR-GFP, a fluorescent marker for transcriptionally-induced overtwisted DNA.
• Live imaging and quantitative analysis of rDNA array spatial organization in Schizosaccharomyces pombe.
• Screening of a deletion mutant collection to identify genes affecting rDNA organization.

Main Results:

• rDNA array spatial organization is dynamic and influenced by cell cycle, glucose starvation, RNA pol I inhibition, and TOR activation.
• Deletions in large ribosomal protein (RPL) genes alter rDNA organization.
• RPL gene deletion mutants exhibit resistance to the TOR inhibitor Torin1, involving pathways like MAPK Pmk1.

Conclusions:

• Altered rDNA morphology in RPL deletion mutants suggests compensatory ribosome biogenesis changes.
• Multiple signaling pathways contribute to compensatory responses.
• These findings may inform understanding of human diseases like ribosomopathies.