PXD044446

PXD044446 is an original dataset announced via ProteomeXchange.

Title	The MYCN oncoprotein is an RNA-binding protein that promotes nascent RNA turnover via the NEXT targeting complex of the nuclear exosome
Description	The MYCN oncoprotein forms a DNA-binding heterodimer with its partner protein MAX. MYCN-driven tumor cells depend on the nuclear exosome, a 3`-5` RNA exonuclease complex, to progress through S phase. Here we show that MYCN forms stable high molecular weight complexes with the nuclear exosome and additional RNA-binding proteins. Enhanced cross-linking and immunoprecipitation (eCLIP) experiments reveal that MYCN binds to thousands of sites on RNA, mainly localized in introns. MYCN directly binds RNA with a preference for UG-rich sequences via a short, highly conserved sequence motif termed MycBox I. Upon exosome inhibition, MYCN relocalizes globally from promoters to intronic RNAs; at promoters, MYCN is then replaced by the repressive MXD6 (MNT) protein, leading to the recruitment of histone deacetylase complexes and inhibition of MYCN-dependent transcription. MYCN is tightly associated with the exosome targeting complex NEXT and promotes the degradation of non-polyadenylated RNA at its bound introns. Our data demonstrate that MYCN is an RNA-binding protein that controls nascent RNA turnover and argue that the competition between RNA- and DNA-bound states of MYCN links the dynamics of the MYCN/MAX/MXD network to the completion of mRNA processing.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:50:53.861.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Petra Beli
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-08 03:46:17	ID requested
1	2024-07-18 15:45:43	announced
⏵ 2	2024-10-22 06:50:54	announced	2024-10-22: Updated project metadata.

10.1016/j.molcel.2024.04.007;

Papadopoulos D, Ha SA, Fleischhauer D, Uhl L, Russell TJ, Mikicic I, Schneider K, Brem A, Valanju OR, Cossa G, Gallant P, Schuelein-Voelk C, Maric HM, Beli P, B, ü, chel G, Vos SM, Eilers M, The MYCN oncoprotein is an RNA-binding accessory factor of the nuclear exosome targeting complex. Mol Cell, 84(11):2070-2086.e20(2024) [pubmed]

submitter keyword: neuroblastoma, exosome,MYCN, NEXT, MXD, ZCCHC8, MYC, intron, MAX, MNT, eCLIP

Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
lab head
Petra Beli
contact affiliation	Institute of Molecular Biology (IMB), Mainz, Germany
contact email	p.beli@imb-mainz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/07/PXD044446

PRIDE project URI

• PRIDE
  1. PXD044446
     1. Label: PRIDE project
     2. Name: The MYCN oncoprotein is an RNA-binding protein that promotes nascent RNA turnover via the NEXT targeting complex of the nuclear exosome