PXD053881-2

PXD053881 is an original dataset announced via ProteomeXchange.

Title	Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2’O-methylation
Description	Mechanistic studies have revealed that TLR8 senses single-stranded RNA (ssRNA) fragments, processed via synergistic cleavage by ribonucleases (RNase) T2 and RNase A family members. Processing by these RNases releases uridines and purine-terminated residues resulting in TLR8 activation. Monocytes show high expression of RNase 6, yet this RNase has not been analyzed for its physiological contribution to recognition of bacterial RNA by TLR8. Herein, we characterized molecular RNase 6 cleavage mechanisms. BLaER1 RNASE6-/- cells showed a dampened TLR8-dependent response upon stimulation with isolated bacterial RNA (bRNA) but also upon infection with live whole bacteria. Pretreatment of bacterial RNA with recombinant RNase 6 generated fragments that induced stimulation in RNASE6 knockout cells. 2’O-RNA methyl modification, when introduced at the first uridine in the UA dinucleotide, impaired upstream processing by RNase 6 and dampened TLR8 stimulation. In summary, this data shows that RNase 6 plays a critical role in the processing of bacterial RNA by generating uridine-terminated breakdown products that ultimately activate TLR8.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:58:05.711.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	F Butter
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480; timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2024-07-11 04:41:07	ID requested
1	2024-09-12 00:52:45	announced
⏵ 2	2024-10-22 06:58:06	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: LC-MS/MS

Falk Butter
contact affiliation	Institute of Molecular Biology (IMB)
contact email	f.butter@imb.de
lab head
F Butter
contact affiliation	Quantitative Proteomics Institute of Molecular Biology (IMB)
contact email	f.butter@imb-mainz.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD053881
     1. Label: PRIDE project
     2. Name: Bacterial RNA sensing by TLR8 requires RNase 6 processing and is inhibited by RNA 2’O-methylation