Ribosome Molecular Aging Shapes Translation Dynamics

Area of Science:

• Molecular Biology
• Cellular Biology
• Aging Research

Background:

• Cellular homeostasis requires component renewal, but some complexes like ribosomes have long lifespans.
• The functional impact of extended molecular age on cellular components, particularly ribosomes, remains unclear.

Purpose of the Study:

• To develop a method for mapping the life stages of biomolecules within cells.
• To investigate how the age of ribosomes affects their function and translational dynamics.

Main Methods:

• Developed a spatiotemporal mapping strategy to track ribosome age and location.
• Analyzed ribosome function, including elongation, pausing, and termination, based on molecular age.
• Profiled ribosomal RNA modifications to assess age-related changes.
• Utilized pulse-chase labeling in *C. elegans* to study ribosome aging *in vivo*.

Main Results:

• Intracellular ribosome aging alters translational dynamics for specific transcripts.
• Aged ribosomes show impaired elongation at basic amino acid-rich sequences, causing pausing and premature termination.
• Molecular aging increases ribosome collision propensity in specific subpopulations.
• Enrichment of aged ribosomes amplifies age-dependent translation defects.
• *In vivo* studies in aged *C. elegans* confirmed aged ribosomes influence translational dynamics during organismal aging.

Conclusions:

• Ribosome molecular age is a key determinant of translational dynamics.
• Aging of ribosomes, a core gene-expression complex, is linked to organismal aging.
• The developed pulse-chase strategy maps macromolecular demographics in space and time.