PXD072588

PXD072588 is an original dataset announced via ProteomeXchange.

Title	Composite SMG5-1 SMG6 PIN domain formation is essential for NMD
Description	Nonsense-mediated mRNA decay (NMD) relies on the coordinated assembly and action of multiple protein factors. Degradation of target mRNAs begins with endonucleolytic cleavage near premature stop codons, but the mechanisms of endonuclease activation and regulation remain unclear. Using structural predictions, biochemical in vitro assays, and cell-based NMD analysis, we show that SMG5 and SMG6 interact via their PIN domains to form a composite interface (cPIN) with full endonuclease activity. In vitro reconstituted SMG5-SMG6 cPIN heterodimers show high activity, as SMG5 completes the SMG6 active site and substrate binding site. Mutations in residues at their predicted interaction surfaces, RNA-binding sites, or active-site attenuate or abolish cPIN activity in vitro and impair cellular NMD. Our findings demonstrate how paralogous PIN domains complement each other to assemble a highly active endonuclease in NMD, providing a structural and mechanistic explanation for efficient NMD substrate degradation.
HostingRepository	PRIDE
AnnounceDate	2026-01-30
AnnouncementXML	Submission_2026-01-30_05:08:22.002.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: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-02 14:37:28	ID requested
⏵ 1	2026-01-30 05:08:22	announced

Dataset with its publication pending

submitter keyword: Nonsense-mediated mRNA decay

Elena Conti
contact affiliation	Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried, 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/2026/01/PXD072588

PRIDE project URI

• PRIDE
  1. PXD072588
     1. Label: PRIDE project
     2. Name: Composite SMG5-1 SMG6 PIN domain formation is essential for NMD