Ribosomal biogenesis defects trigger subunit specific developmental checkpoints via TOR signaling and gap junction in...

Area of Science:

• Developmental Biology
• Molecular Genetics
• Cell Biology

Background:

• Ribosome biogenesis is essential for postembryonic development in *Caenorhabditis elegans*.
• Compromised ribosome production leads to developmental arrest, but the specific mechanisms and checkpoints involved are not fully understood.
• Maternally supplied ribosomes enable embryonic development, but de novo production is critical for larval stages.

Purpose of the Study:

• To compare the developmental consequences of defects in large ribosomal subunit genes, small ribosomal subunit genes, and rRNA synthesis.
• To investigate the molecular pathways and checkpoints involved in ribosome biogenesis-related developmental arrests.
• To elucidate the distinct roles of different ribosomal components in coordinating postembryonic development.

Main Methods:

• Comparative analysis of null mutants for large (rpl-5, rpl-33) and small (rps-10, rps-23) ribosomal subunit genes, and rRNA synthesis mutants (rpoa-2, rDNA loci).
• Tracking of mesoblast (M) cell divisions to assess proliferation arrests.
• Gene expression analysis to identify molecular responses to ribosomal defects.
• Genetic interaction studies involving gap junction proteins (INX-14) and TOR pathway components (SINH-1, TORC1/TORC2 kinases).

Main Results:

• Large ribosomal subunit mutations induced a stringent M cell proliferation arrest, more severe than small subunit or rRNA synthesis defects.
• The observed arrest was CKI-1-independent, suggesting a novel checkpoint mechanism.
• Distinct gene expression profiles were observed: large subunit and rDNA mutants overexpressed rRNA processing/assembly genes, while RPOA-2 mutants overexpressed lipid metabolism genes.
• Gap junction protein INX-14 and TORC2 component SINH-1 partially suppressed M cell arrest in small subunit mutants but not large subunit mutants.
• TOR pathway kinases modulated growth arrest in RPOA-2 depleted backgrounds, indicating convergence of gap junction and TOR signaling on a ribosomal stress checkpoint.

Conclusions:

• Loss of large ribosomal subunit genes triggers a unique, CKI-1-independent developmental arrest in *C. elegans*.
• Distinct signaling pathways, including gap junction communication and TOR signaling, converge on a ribosomal stress checkpoint.
• These findings reveal how different defects in ribosome biogenesis are differentially sensed and coordinated to regulate postembryonic development.