BRAT1 links Integrator and defective RNA processing with neurodegeneration

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00566109" target="_blank" >RIV/68378050:_____/22:00566109 - isvavai.cz</a>

Alternative codes found

RIV/86652036:_____/22:00566109 RIV/00216208:11310/22:10454425

Result on the web

<a href="https://www.nature.com/articles/s41467-022-32763-6" target="_blank" >https://www.nature.com/articles/s41467-022-32763-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-022-32763-6" target="_blank" >10.1038/s41467-022-32763-6</a>

Result language

angličtina

Original language name

BRAT1 links Integrator and defective RNA processing with neurodegeneration

Original language 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 tightly interacts with INTS9/INTS11 subunits of the Integrator complex that processes 3' ends of various noncoding RNAs and pre-mRNAs. We find that Integrator functions are disrupted by BRAT1 deletion. In particular, defects in BRAT1 impede proper 3' end processing of UsnRNAs and snoRNAs, replication-dependent histone pre-mRNA processing, and alter the expression of protein-coding genes. Importantly, impairments in Integrator function are also evident in patient-derived cells from BRAT1 related neurological disease. Collectively, our data suggest that defects in BRAT1 interfere with proper Integrator functions, leading to incorrect expression of RNAs and proteins, resulting in neurodegeneration.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2022

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Nature Communications

ISSN

2041-1723

e-ISSN

2041-1723

Volume of the periodical

13

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

5026

UT code for WoS article

000845881900001

EID of the result in the Scopus database

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