S-phase AURORA A interacts with DICER and SETD2 to maintain cell cycle progression
The aim of this study is to investigate the non-catalytic functions of AURORA A during S-phase in non-neuroblastoma cells. Using a combination of biochemical assays, next generation sequencing and proteomics, we identified an extensive network of AURORA A-interacting proteins that assembles during S-phase in acute myeloid leukemia (AML) cells. The S-phase interactome of AURORA A is notably enriched in RNA-binding proteins. Using gradient centrifugation, we demonstrated that the ribonuclease DICER and the histone methyltransferase SETD2 require RNA to be integrated into these complexes. PROTAC-induced degradation of AURORA A disrupts this association, leading to the dissociation of SETD2 from chromatin, together resulting in S-phase defects.
The aim of this study is to investigate the non-catalytic functions of AURORA A during S-phase in non-neuroblastoma cells. Using a combination of biochemical assays, next generation sequencing and proteomics, we identified an extensive network of AURORA A-interacting proteins that assembles during S-phase in acute myeloid leukemia (AML) cells. The S-phase interactome of AURORA A is notably enriched in RNA-binding proteins. Using gradient centrifugation, we demonstrated that the ribonuclease DICER and the histone methyltransferase SETD2 require RNA to be integrated into these complexes. PROTAC-induced degradation of AURORA A disrupts this association, leading to the dissociation of SETD2 from chromatin, together resulting in S-phase defects.
Biochemical Institute - Christian-Albrechts-University Kiel