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Series GSE152850 Query DataSets for GSE152850
Status Public on Nov 09, 2021
Title Ageing-dependent ribosome pausing and nascent polypeptide aggregation
Organisms Saccharomyces cerevisiae; Caenorhabditis elegans
Experiment type Other
Summary Increased protein misfolding and aggregation are key hallmarks of ageing and many age-related diseases. As generating and maintaining a functional proteome (proteostasis) is crucial to every cellular process, this age-related decline in proteostasis is suggested to play a primary role in the breakdown of diverse cellular subsystems during ageing. Indeed, augmented proteostasis pathways are associated with extended lifespan across different species. With the ribosome as the earliest proteostasis checkpoint, decreased protein synthesis is also a conserved mechanism that extends lifespan. Yet, it remains unclear whether ageing impacts translation after initiation. Here, we use worms and yeast to investigate how ageing influences translation elongation. We show an age-dependent increase in ribosome pausing at diverse positions in coding sequences. This pausing is conserved in both worms and yeast, particularly at Arg and polybasic regions. We further show that such pausing is associated with the age-dependent aggregation of truncated nascent proteins involved in proteostasis pathways, notably aminoacyl tRNA synthetases. Moreover, we find that impairment in clearing truncated nascent proteins is associated with decreased lifespan. These data establish elongation kinetics and co-translational quality control as critical contributors of the age-related proteostasis collapse, which may precipitate the systemic decline observed during ageing.
 
Overall design Replicate ribosome profiling libraries were prepared during ageing of worms and yeast, including the long-lived sch9Δ yeast strain.
 
Contributor(s) Stein KC, Frydman J
Citation(s) 35046576
Submission date Jun 19, 2020
Last update date Jan 28, 2022
Contact name Kevin C. Stein
E-mail(s) kcstein@stanford.edu
Organization name Stanford University
Department Biology
Lab Frydman
Street address Clark Center E200, 318 Campus Drive
City Stanford
State/province California
ZIP/Postal code 94305
Country USA
 
Platforms (2)
GPL21656 Illumina HiSeq 4000 (Saccharomyces cerevisiae)
GPL22765 Illumina HiSeq 4000 (Caenorhabditis elegans)
Samples (17)
GSM4627275 N2_Day1_Rep1
GSM4627276 N2_Day1_Rep2
GSM4627277 N2_Day6
Relations
BioProject PRJNA640641
SRA SRP268024

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE152850_RAW.tar 304.3 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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