AURORA A interacts with DICER and SETD2 and promotes S-phase progression

ABSTRACT: The oncogenic kinase AURORA A is essential for mitotic progression, and its catalytic inhibition arrests cells at the G2/M-transition. Unexpectedly, degradation of AURORA A by PROTACs (proteolysis targeting chimeras) induces profound S-phase defects, revealing a non-catalytic scaffolding function of AURORA A. To dissect this function, we profiled the AURORA A S-phase interactome and identified multiple RNA-binding proteins not characterized as AURORA A substrates. Among these, the ribonuclease DICER directly associates with AURORA A to form an abundant nuclear complex. RNA degradation shifted AURORA A, DICER, and additional RNA-binding proteins from heavy to light gradient fractions, implicating RNA-dependent complex function. In contrast, PROTAC-mediated depletion of AURORA A altered the gradient migration behavior and chromatin association of the histone methyltransferase SETD2. These findings reveal a dual-output model for the S-phase AURORA A complex: First, RNA-binding proteins are recruited to R-loops, which may arise from transcription-replication conflicts. DICER then processes the R-loop, while AURORA A simultaneously recruits SETD2. This coordinated action prevents the stressed region from being disrupted by spurious transcription, thereby facilitating efficient resolution of replicative stress.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Cell Suspension Culture

DISEASE(S): Acute Leukemia

SUBMITTER: Nicola Berner  

LAB HEAD: Bernhard Kuster

PROVIDER: PXD076528 | Pride | 2026-07-01

REPOSITORIES: Pride