PXD049474

PXD049474 is an original dataset announced via ProteomeXchange.

Title	UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2
Description	Nonsense-mediated mRNA decay (NMD) is a conserved co-translational mRNA surveillance and turnover pathway across eukaryotes. NMD has a central role in degrading defective mRNAs and also regulates the stability of a significant portion of the transcriptome. The pathway is organized around UPF1, an RNA helicase that can interact with several NMD-specific factors. In human cells, degradation of the targeted mRNAs begins with a cleavage event that requires the recruitment of the SMG6 endonuclease to UPF1. Previous studies have identified functional links between SMG6 and UPF1, but the underlying molecular mechanisms have remained elusive. In this work, we used mass spectrometry, structural biology and biochemical approaches to identify and characterize a conserved short linear motif in SMG6 that interacts with the cysteine/histidine-rich (CH) domain of UPF1. Unexpectedly, we found that the UPF1-SMG6 interaction is precluded when the UPF1 CH domain is engaged with another NMD factor, UPF2. Based on cryo-EM data, we propose that the formation of distinct SMG6-containing and UPF2-containing NMD complexes may be dictated by the RNA-binding status of UPF1. Our findings rationalize a key event in the metazoan NMD quality control pathway and progress our understanding of mechanisms regulating activity and guiding substrate recognition by the SMG6 endonuclease.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:37:54.763.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Barbara Steigenberger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2024-02-19 02:36:28	ID requested
1	2024-05-01 13:39:48	announced
⏵ 2	2024-10-22 06:37:55	announced	2024-10-22: Updated project metadata.

10.1093/NAR/GKAE323;

submitter keyword: RNA,Nonsense-mediated mRNA decay (NMD), UPF1

Elena Conti
contact affiliation	Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried/Munich, Germany
contact email	conti@biochem.mpg.de
lab head
Barbara Steigenberger
contact affiliation	MPI of Biochemistry
contact email	steigenberger@biochem.mpg.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/2024/05/PXD049474

PRIDE project URI

• PRIDE
  1. PXD049474
     1. Label: PRIDE project
     2. Name: UPF1 helicase orchestrates mutually exclusive interactions with the SMG6 endonuclease and UPF2