PXD039956

PXD039956 is an original dataset announced via ProteomeXchange.

Title	A combinatorial approach to uncover a novel Integrator subunit
Description	RNA polymerase II (RNAPII) controls the expression of all protein coding genes and most noncoding loci in higher eukaryotes. The ultimate rate of transcription is regulated at the level of multiple checkpoints during the transcription cycle (initiation, pausing, termination). Calibrating the activity of RNAPII is fundamental to all cellular processes and requires an assortment of polymerase-associated factors that are recruited at sites of active transcription. The Integrator complex is one of the most elusive transcriptional regulators in metazoans, deemed to be recruited after initiation to help establish and modulate paused RNAPII. Recent structural, biochemical, and functional evidence suggest that Integrator is composed of 14 subunits that assemble and operate in a modular fashion. We employed proteomics and machine-learning structure prediction (AlphaFold2) approaches to identify a novel Integrator subunit, INTS15. We report that INTS15 assembles primarily with the INTS13/INTS14/INTS10 module and interfaces with the core of the Int-PP2A complex. Functional genomics analysis further reveals a role for INTS15 in modulating RNAPII pausing at a subset of genes in human cell lines. Our study shows that omics approaches combined with AlphaFold2-based predictions provide novel insights into the molecular architecture of large and flexible multiprotein complexes.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:03:17.902.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Frank Stein
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-08 06:30:30	ID requested
1	2023-07-20 11:20:37	announced
⏵ 2	2023-11-14 09:03:18	announced	2023-11-14: Updated project metadata.

Offley SR, Pfleiderer MM, Zucco A, Fraudeau A, Welsh SA, Razew M, Galej WP, Gardini A, A combinatorial approach to uncover an additional Integrator subunit. Cell Rep, 42(3):112244(2023) [pubmed]

submitter keyword: transcription, proteomics,Integrator complex, functional genomics, AlphaFold2

Wojciech Galej
contact affiliation	European Molecular Biology Laboratory 71 Av. des Martyrs, 38000 Grenoble France
contact email	wgalej@embl.gr
lab head
Frank Stein
contact affiliation	EMBL
contact email	frank.stein@embl.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/2023/07/PXD039956

PRIDE project URI

• PRIDE
  1. PXD039956
     1. Label: PRIDE project
     2. Name: A combinatorial approach to uncover a novel Integrator subunit