PXD035092

PXD035092 is an original dataset announced via ProteomeXchange.

Title	THOC5 complexes with other proteins (DDX5, DDX17 and CDK12) essential in primitive cell survival to regulate R loop structures and RNA elongation rate.
Description	THOC5, a member of the THO complex, is essential for the 3´processing of some inducible genes, the export of a subset of genes and stem cell self-renewal. Utilising nanopore mRNA-sequencing we show that when THOC5 is depleted 50% of mRNAs undergo altered 3´end cleavage. Further, THOC5 depletion leads to increased RNA Polymerase II (Pol II) presence on the gene body and close to the 3’end. Moreover, THOC5 is recruited close to high density Pol II sites except those at the promotor regions suggesting that THOC5 is involved in transcriptional elongation. Indeed, THOC5 independent genes in cells expressing fast Pol II became THOC5 dependent in cells expressing slow Pol II. In cells expressing slow Pol II chromatin associated THOC5 interacts with CDK12 (a protein that modulates mRNA elongation rates), RNA helicases DDX5, DDX17, and THOC6. Importantly these interactions were not observed in cells expressing fast Pol II. The CDK12/THOC5 interaction promotes CDK12 recruitment to R-loops in a THOC6-dependent manner. These data demonstrate that THOC5/THOC6 play a part in transcription elongation. Given the role of THOC5 in primitive cell survival its phosphorylation by agonists, oxidative stress and oncogenes the pathway we identified has relevance in the physiology and pathology of stem cells
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:56:08.282.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Bethany Geary
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-05 05:31:38	ID requested
1	2022-12-12 08:21:20	announced
⏵ 2	2023-11-14 08:56:08	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: RNA sequencing using nanopore technology, Pol II elongation rate,mRNA export protein THOC5, R-loop

Bethany Geary
contact affiliation	Stem Cell and Leukemia Protoemics Laboratory, Division of Cancer Sciences, University of Manchester, M20 3LJ, UK
contact email	bethany.geary@manchester.ac.uk
lab head
Bethany Geary
contact affiliation	University of Manchester
contact email	bethany.geary@manchester.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035092
     1. Label: PRIDE project
     2. Name: THOC5 complexes with other proteins (DDX5, DDX17 and CDK12) essential in primitive cell survival to regulate R loop structures and RNA elongation rate.