PXD076528

PXD076528 is an original dataset announced via ProteomeXchange.

Title	AURORA A interacts with DICER and SETD2 and promotes S-phase progression
Description	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.
HostingRepository	PRIDE
AnnounceDate	2026-07-01
AnnouncementXML	Submission_2026-07-01_03:00:04.010.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nicola Berner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral; timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2026-04-02 14:55:12	ID requested
⏵ 1	2026-07-01 03:00:04	announced

10.1038/S44319-026-00850-0;

submitter keyword: DICER, AURKA, R-Loops,AURORA A, PROTACs

Bernhard Kuster
contact affiliation	School of Life Sciences, Technical University of Munich, Freising, Germany
contact email	kuster@tum.de
lab head
Nicola Berner
contact affiliation	German Cancer Consortium (DKTK), Germany Chair of Proteomics and Bioanalytics Technical University of Munich (TUM), Freising, Germany German Cancer Research Center (DKFZ), Heidelberg, Germany
contact email	n.berner@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD076528
     1. Label: PRIDE project
     2. Name: AURORA A interacts with DICER and SETD2 and promotes S-phase progression