Sequestration of ribosomal subunits as inactive 80S by targeting eIF6 limits mitotic exit and cancer progression
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ABSTRACT:
PROVIDER: PRJNA1137263 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29874567.fastq.gz | Fastqsanger.gz | |||
| SRR29874568.fastq.gz | Fastqsanger.gz | |||
| SRR29874569.fastq.gz | Fastqsanger.gz | |||
| SRR29874570.fastq.gz | Fastqsanger.gz | |||
| SRR29874571.fastq.gz | Fastqsanger.gz |
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Project description:Moderating the pool of active ribosomal subunits is critical for maintaining global translation rates. A crucial factor for modulating the 60S ribosomal subunits is eukaryotic translation initiation factor 6. Release of eIF6 from 60S is essential to permit 60S interactions with 40S. Here, using the N106S mutant of eIF6, we show that disrupting eIF6 interaction with 60S leads to an increase in vacant 80S. It further highlights a dichotomy in the anti-association activity of eIF6 that is distinct from its role in 60S biogenesis and shows that the nucleolar localization of eIF6 is not dependent on uL14-BCCIP interactions. Limiting active ribosomal pools markedly deregulates translation especially in mitosis and leads to chromosome segregation defects, mitotic exit delays and mitotic catastrophe. Ribo-Seq analysis of the eIF6-N106S mutant shows a significant downregulation in the translation efficiencies of mitotic factors and specifically transcripts with long 3′UTRs. eIF6-N106S mutation also limits cancer invasion, and this role is correlated with the overexpression of eIF6 only in high-grade invasive cancers suggesting that deregulation of eIF6 is probably not an early event in cancers. Thus, this study highlights the segregation of eIF6 functions and its role in moderating 80S availability for mitotic translation and cancer progression.
2024-12-04 | GSE272516 | GEO
Project description:Moderating the pool of active ribosomal subunits is critical for maintaining global translation rates. A crucial factor for modulating the 60S ribosomal subunits is eukaryotic translation initiation factor 6. Release of eIF6 from 60S is essential to permit 60S interactions with 40S. Here, using the N106S mutant of eIF6, we show that disrupting eIF6 interaction with 60S leads to an increase in vacant 80S. It further highlights a dichotomy in the anti-association activity of eIF6 that is distinct from its role in 60S biogenesis and shows that the nucleolar localization of eIF6 is not dependent on uL14-BCCIP interactions. Limiting active ribosomal pools markedly deregulates translation especially in mitosis and leads to chromosome segregation defects, mitotic exit delays and mitotic catastrophe. Ribo-Seq analysis of the eIF6-N106S mutant shows a significant downregulation in the translation efficiencies of mitotic factors and specifically transcripts with long 3′UTRs. eIF6-N106S mutation also limits cancer invasion, and this role is correlated with the overexpression of eIF6 only in high-grade invasive cancers suggesting that deregulation of eIF6 is probably not an early event in cancers. Thus, this study highlights the segregation of eIF6 functions and its role in moderating 80S availability for mitotic translation and cancer progression.
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Project description:Sequestration of ribosomal subunits as inactive 80S by targeting eIF6 limits mitotic exit and cancer progression
| PRJNA1137264 | ENA
Project description:Moderating the pool of active ribosomal subunits is critical for maintaining global translation rates. A factor crucial for modulating the 60S ribosomal subunit is eukaryotic translation initiation factor-6 (eIF6). Release of eIF6 from the 60S subunit is essential to permit 60S interactions with the 40S subunit. Here, using the eIF6-N106S mutant, we show that disrupting eIF6 interaction with the 60S subunit leads to an increase in vacant 80S ribosomes. It further highlights a dichotomy in the anti-association activity of eIF6 that is distinct from its role in 60S subunit biogenesis and shows that nucleolar localization of eIF6 is not dependent on BCCIP chaperone and uL14. Limiting active ribosomal pools markedly deregulates translation especially in mitosis and leads to chromosome segregation defects, mitotic exit delays and mitotic catastrophe. Ribo-seq analysis of eIF6-N106S mutant shows a significant downregulation in the translation efficiencies of mitotic factors and specifically transcripts with long 3' untranslated regions. eIF6-N106S mutation also limits cancer invasion, and this role is correlated with overexpression of eIF6 only in high-grade invasive cancers suggesting that deregulation of eIF6 is probably not an early event in cancers. Thus, this study highlights the segregation of eIF6 functions and its role in moderating 80S ribosome availability for translation, mitosis and cancer progression.
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