Human SKI component SKIV2L regulates telomeric DNA-RNA hybrids and prevents telomere fragility

Super killer (SKI) complex is a well-known cytoplasmic 3'-5' mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs, is implicated with the extraction of mRNA at stalled ribosomes, tackling aberrant translation. Here, we show that SKIV2L and TTC37 of the hSKI complex are present within the nucleus, localize on chromatin and at some telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomere replication stress, independently of its helicase domain, and increases the stability of telomere DNA-RNA hybrids in G2. We further demonstrate that purified hSKI complex binds telomeric DNA and RNA substrates <i>in vitro</i> and SKIV2L association with telomeres is dependent on DNA-RNA hybrids. Taken together, our results provide a nuclear function for SKIV2L of the hSKI complex in overcoming replication stress at telomeres mediated by its recruitment to DNA-RNA hybrid structures in G2 and thus maintaining telomere stability.

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Journal
iScience
Published
2024-10-04
DOI
https://doi.org/10.1016/j.isci.2024.111096
Primary Topic
Telomeres, Telomerase, and Senescence
Type
article
Field-Weighted Citation Impact
0.00

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article

Human SKI component SKIV2L regulates telomeric DNA-RNA hybrids and prevents telomere fragility

Almutasem Saleh, Emilia Herrera‐Moyano, Rosa María Porreca, Roser Gonzalez-Franco et al.
iScience
Telomeres, Telomerase, and Senescence
article

Human SKI component SKIV2L regulates telomeric DNA-RNA hybrids and prevents telomere fragility

Almutasem Saleh, Emilia Herrera‐Moyano, Rosa María Porreca, Roser Gonzalez-Franco, Lepakshi Ranjha, Eleni Skourti, Alex Montoya, Holger Kramer, Emmanouil Stylianakis, Jean‐Baptiste Vannier, Ying Sun, Ruihan Li
article en

Abstract

Super killer (SKI) complex is a well-known cytoplasmic 3'-5' mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs, is implicated with the extraction of mRNA at stalled ribosomes, tackling aberrant translation. Here, we show that SKIV2L and TTC37 of the hSKI complex are present within the nucleus, localize on chromatin and at some telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomere replication stress, independently of its helicase domain, and increases the stability of telomere DNA-RNA hybrids in G2. We further demonstrate that purified hSKI complex binds telomeric DNA and RNA substrates <i>in vitro</i> and SKIV2L association with telomeres is dependent on DNA-RNA hybrids. Taken together, our results provide a nuclear function for SKIV2L of the hSKI complex in overcoming replication stress at telomeres mediated by its recruitment to DNA-RNA hybrid structures in G2 and thus maintaining telomere stability.

iScienceVol. 27(11)
Hammersmith Hospital (GB), MRC London Institute of Medical Sciences (GB), Imperial College London (GB)
Universidad de Sevilla, UK Research and Innovation, Imperial College London, Horizon 2020 Framework Programme, Medical Research Council, European Regional Development Fund, Agencia Estatal de Investigación
Openalex Percentile: Top 76%
Telomeres, Telomerase, and Senescence
DOIOpen Access PDFOpenAlex
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