PXD045912

PXD045912 is an original dataset announced via ProteomeXchange.

Title	Concerted action of RNase T2 and PLD exonucleases in RNA processing for TLR7 activation
Description	Toll-like receptor 7 (TLR7) plays a key role in the recognition of RNA viruses and the subsequent induction of an innate immune response. TLR7 contains two ligand binding pockets that recognize distinct RNA degradation products: Pocket 1 recognizes guanosine nucleotides and pocket 2 coordinates short, pyrimidine-rich RNA fragments, while the engagement of both pockets is required to activate TLR7. How these ligands are generated within the endolysosomal compartment is currently unknown. Using a pDC cell line, we here show that the endonuclease RNase T2 and the 5' exonucleases PLD3 and PLD4 act in concert to produce these ligands. On the one hand, RNase T2 generates 2',3'-cyclophosphate-guanosine terminated RNA fragments upon which PLD exonuclease activity acts to release the terminal 2',3'-cyclic GMP. This molecule serves as the physiological ligand for the first binding pocket. On the other hand, PLD activity is also required to generate short RNA fragments that occupy the second binding pocket of TLR7. While PLD3 and PLD4 exert comparable catalytic activities, the almost exclusive expression of PLD4 in pDCs suggests that PLD4 is the relevant exonuclease for pDC activation in the human system. Biochemical and structural studies of PLD3 and PLD4 show that these enzymes form homodimers with two ligand binding sites. Dimer formation is critical for catalytic activity, and previously identified disease-associated mutants fail to form stable dimers. In conclusion, our data provide a mechanistic basis for the recognition of RNA fragments by TLR7.
HostingRepository	PRIDE
AnnounceDate	2024-06-19
AnnouncementXML	Submission_2024-06-19_02:11:39.003.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jan Bernd Stöckl
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-05 07:08:39	ID requested
⏵ 1	2024-06-19 02:11:39	announced

10.1016/J.IMMUNI.2024.04.010;

submitter keyword: toll-like receptor,Proteomics, nuclease, LC-MS/MS

Thomas Fröhlich
contact affiliation	Ludwig-Maximilians-Universität München Genzentrum Laboratory for Functional Genome Analysis Feodor-Lynen-Str. 25 D-81377 München
contact email	frohlich@genzentrum.lmu.de
lab head
Jan Bernd Stöckl
contact affiliation	Genzentrum der LMU München
contact email	stoeckl@genzentrum.lmu.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/2024/06/PXD045912

PRIDE project URI

• PRIDE
  1. PXD045912
     1. Label: PRIDE project
     2. Name: Concerted action of RNase T2 and PLD exonucleases in RNA processing for TLR7 activation