PT  - JOURNAL ARTICLE
AU  - Emilia Herrera-Moyano
AU  - Rosa Maria Porreca
AU  - Lepakshi Ranjha
AU  - Eleni Skourti
AU  - Roser Gonzalez-Franco
AU  - Ying Sun
AU  - Emmanouil Stylianakis
AU  - Alex Montoya
AU  - Holger Kramer
AU  - Jean-Baptiste Vannier
TI  - The human SKI complex prevents DNA-RNA hybrid-associated telomere instability
AID  - 10.1101/2020.05.20.107144
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2020.05.20.107144
4099  - http://biorxiv.org/content/early/2021/01/28/2020.05.20.107144.short
4100  - http://biorxiv.org/content/early/2021/01/28/2020.05.20.107144.full
AB  - Super killer (SKI) complex is a well-known cytoplasmic 3′ to 5′ mRNA decay complex that functions with the exosome to degrade excessive and aberrant mRNAs. Recently, SKIV2L, the 3′ to 5′ RNA helicase of the human SKI (hSKI) complex has been implicated in the degradation of nuclear non-coding RNAs escaping to the cytoplasm. Here, we show that hSKI is present in the nucleus, on chromatin and in particular at telomeres during the G2 cell cycle phase. In cells, SKIV2L prevents telomeric loss, and DNA damage response activation, and its absence leads to DNA-RNA hybrid-mediated telomere fragility. Moreover, we demonstrate that purified hSKI complex preferentially unwinds telomeric DNA-RNA hybrids in vitro. Taken together, our results provide a nuclear function of the hSKI complex in overcoming replication stress caused by aberrant processing of telomeric DNA-RNA hybrids and thus maintaining telomere stability.Competing Interest StatementThe authors have declared no competing interest.