PXD070077

PXD070077 is an original dataset announced via ProteomeXchange.

Title	Molecular mechanisms of recruitment, function and regulation of the RNA helicase UPF1 in replication-dependent histone mRNA decay
Description	Metazoan histone mRNAs are a unique class of mRNAs that lack the poly(A) tail present in all other eukaryotic transcripts. Instead, they end in a conserved stem-loop (SL) structure, necessitating a decay mechanism that is distinct from deadenylation-initiated degradation. Here, combining cryoEM with chemical crosslinking mass spectrometry (CXMS) and functional approaches, we elucidate molecular mechanisms of initiation of histone mRNA decay. At the end of S-phase, the RNA helicase UPF1, the exoribonuclease 3’hExo and stem-loop binding protein SLBP all contribute to histone mRNA degradation, although how they are mechanistically coupled remained unknown. The cryoEM structure of an UPF1:SL RNA complex, presented here, shows that binding of UPF1 partially melts the RNA stem in the absence of ATP, harnessing the free energy derived from RNA-binding to unwind RNA. This melting event primes the SL-RNA for decay by 3’hExo. Using biochemical and cellular analyses, we demonstrate that SLBP directly engages the UPF1 helicase core to attenuate its unwinding activity and prevent premature degradation. Activation of UPF1 at a later stage promotes SL-RNA decay. We provide direct evidence that UPF1, SLBP and 3’hExo form a degradosome-like assembly that functionally couples SL unwinding and degradation, highlighting a dynamic and intricate network of UPF1-centric interactions that orchestrates timely histone mRNA decay.
HostingRepository	PRIDE
AnnounceDate	2025-12-08
AnnouncementXML	Submission_2025-12-08_06:39:55.797.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Olexandr Dybkov
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-30 00:24:36	ID requested
⏵ 1	2025-12-08 06:39:56	announced

Dataset with its publication pending

submitter keyword: exoribonuclease 3’hExo, CXMS, RNA helicase UPF1, cryoEM,histone mRNA decay, SLBP

Henning Urlaub
contact affiliation	Research Group Bioanalytical Mass Spectrometry, Max Planck Institute for Multidisciplinary Sciences, Germany. Bioanalytics, Department of Clinical Chemistry, University Medical Center Goettingen, Germany.
contact email	henning.urlaub@mpinat.mpg.de
lab head
Olexandr Dybkov
contact affiliation	Max Planck Institute for Multidisciplinary Sciences
contact email	odybkov@gwdg.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/2025/12/PXD070077

PRIDE project URI

• PRIDE
  1. PXD070077
     1. Label: PRIDE project
     2. Name: Molecular mechanisms of recruitment, function and regulation of the RNA helicase UPF1 in replication-dependent histone mRNA decay