PXD051452

PXD051452 is an original dataset announced via ProteomeXchange.

Title	Targeting the paralog encoded protein for degradation accounts for the opposite roles of NRBP1 and NRBP2 in regulating LINE1 retrotransposition
Description	The activation of Long Interspersed Nuclear Element 1 (LINE1/L1) retrotransposons not only leads to genome instability, a factor associated with the development of human diseases, but also plays crucial biological roles in fostering genetic diversity and neuronal functions. Therefore, investigating the regulatory mechanisms that have co-evolved to enable the context-dependent activation or suppression of L1 is important for comprehending pathogenesis associated with aberrant L1 activity. Here we show that two paralogs encoding the pseudokinases NRBP1 and NRBP2 oppositely regulate L1 retrotransposon, via influencing integrity of the L1 ribonucleoprotein complex. We demonstrate that the antagonism between NRBP1 and NRBP2 is not a result of the competitive mechanism, but rather due to targeting NRBP1 to proteasome-mediated degradation by NRBP2, probably through heterodimer formation between these two closely related proteins. In addition, we show that reduced NRBP2 activity is correlated with elevated innate immune response and occurrence of autoimmune diseases, which could also be induced upon L1 activation. Moreover, our phylogenetic analysis suggests NRBP2gene as a duplication of the ancestral NRBP, indicating that evolutionary pressure has favoured this acquired layer of functional fine-tuning of the precursor gene. In summary, our discovery not only identifies NRBP1 and NRBP2 as novel L1 regulators and implicates their involvement in human pathogenesis, but also provides novel insights into the regulatory details arising from gene duplication events.
HostingRepository	PRIDE
AnnounceDate	2025-06-07
AnnouncementXML	Submission_2025-06-07_08:26:14.022.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Schwarz
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap XL; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-15 09:17:22	ID requested
⏵ 1	2025-06-07 08:26:14	announced

Dataset with its publication pending

submitter keyword: LINE1, retrotransposon, NRBP2,NRBP1

Ralf Baumeister
contact affiliation	Bio3/Bioinformatics and Molecular Genetics, University of Freiburg, 30Schänzlestrasse 1, D-79104 Freiburg, Germany
contact email	ralf.baumeister@biologie.uni-freiburg.de
lab head
Jennifer Schwarz
contact affiliation	European Molecular Biology Laboratory, Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany
contact email	jennifer.schwarz@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/2025/06/PXD051452

PRIDE project URI

• PRIDE
  1. PXD051452
     1. Label: PRIDE project
     2. Name: Targeting the paralog encoded protein for degradation accounts for the opposite roles of NRBP1 and NRBP2 in regulating LINE1 retrotransposition