Papaspyropoulos et al. 2023 (PRJNA933910)

General Details

Title Decoding of translation-regulating entities reveals heterogeneous translation deficiency patterns in cellular senescence
Organism
Number of Samples 5
Release Date 2023/02/11 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP421957
ENA SRP421957
GEO GSE225095
BioProject PRJNA933910

Publication

Title
Authors Papaspyropoulos A, Hazapis O, Altulea A, Polyzou A, Verginis P, Evangelou K, Fousteri M, Papantonis A, Demaria M, Gorgoulis V
Journal Aging cell
Publication Date 2023 Sep
Abstract Cellular senescence constitutes a generally irreversible proliferation barrier, accompanied by macromolecular damage and metabolic rewiring. Several senescence types have been identified based on the initiating stimulus, such as replicative (RS), stress-induced (SIS) and oncogene-induced senescence (OIS). These senescence subtypes are heterogeneous and often develop subset-specific phenotypes. Reduced protein synthesis is considered a senescence hallmark, but whether this trait pertains to various senescence subtypes and if distinct molecular mechanisms are involved remain largely unknown. Here, we analyze large published or experimentally produced RNA-seq and Ribo-seq datasets to determine whether major translation-regulating entities such as ribosome stalling, the presence of uORFs/dORFs and IRES elements may differentially contribute to translation deficiency in senescence subsets. We show that translation-regulating mechanisms may not be directly relevant to RS, however uORFs are significantly enriched in SIS. Interestingly, ribosome stalling, uORF/dORF patterns and IRES elements comprise predominant mechanisms upon OIS, strongly correlating with Notch pathway activation. Our study provides for the first time evidence that major translation dysregulation mechanisms/patterns occur during cellular senescence, but at different rates depending on the stimulus type. The degree at which those mechanisms accumulate directly correlates with translation deficiency levels. Our thorough analysis contributes to elucidating crucial and so far unknown differences in the translation machinery between senescence subsets. © 2023 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
PMC PMC10497830
PMID 37547972
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR23418171 PRJNA933910 Homo sapiens Fibroblast Ribo-Seq 0.0
SRR23418170 PRJNA933910 Homo sapiens Fibroblast Ribo-Seq 0.0
SRR23418169 PRJNA933910 Homo sapiens Fibroblast Ribo-Seq 0.0
SRR23418167 PRJNA933910 Homo sapiens Fibroblast Ribo-Seq 0.0
SRR23418166 PRJNA933910 Homo sapiens Fibroblast Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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