PXD028591

PXD028591 is an original dataset announced via ProteomeXchange.

Title	BRAT1 Links Integrator and Defective RNA Processing with Neurodegeneration
Description	Mutations in BRAT1, encoding BRCA1-associated ATM activator 1, have been associated with neurodevelopmental and neurodegenerative disorders characterized by heterogeneous phenotypes with varying levels of clinical severity. However, the underlying molecular mechanisms of disease pathology remain poorly understood. Here, we show that BRAT1 is a functional component of the RNA processing protein complex, Integrator. BRAT1 interacts with the INTS9/INTS11 heterodimer, the core Integrator cleavage complex that processes the 3’ ends of various non-coding RNAs and pre-mRNAs, and we find that Integrator integrity and function are disrupted by BRAT1 deletion. In particular, defects in BRAT1 impede proper 3’ end processing of UsnRNAs, snoRNAs, and replication-dependent histone mRNAs, and alter expression of protein-coding genes. Importantly, defects in Integrator integrity and function are also evident in patient-derived cells from BRAT1 related neurological disease. Collectively, these data identify BRAT1 as a functional component of Integrator and link defects in this critical endonuclease complex with hereditary neurodegenerative disease.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:53:52.637.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD028591
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Karel Harant
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-09-16 09:00:56	ID requested
1	2022-08-30 02:03:25	announced
⏵ 2	2023-11-14 08:53:53	announced	2023-11-14: Updated project metadata.

10.6019/PXD028591;

submitter keyword: small nuclear RNA,BRAT1, Integrator complex, neurodegeneration

Hana Hanzlikova
contact affiliation	Laboratory of Genome Dynamics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague 4, 142 20, Czech Republic
contact email	hana.hanzlikova@img.cas.cz
lab head
Karel Harant
contact affiliation	Charles University
contact email	harant@natur.cuni.cz
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD028591
     1. Label: PRIDE project
     2. Name: BRAT1 Links Integrator and Defective RNA Processing with Neurodegeneration