Opposing roles of pseudokinases NRBP1 and NRBP2 in regulating L1 retrotransposition

Wei Yang, Shaobo Cong, Ruoyao Li, Jennifer Schwarz, Thilo Schulze, Raban A. Gevelhoff, Xinyan Chen, Sara Ullrich, Kristina Falkenstein, Denis Ott, Pia Eixmann, Angelica Trentino, Antje Thien, Thierry Heidmann, Ekkehard Schulze, Bettina Warscheid, Ralf Baumeister () and Wenjing Qi ()
Additional contact information
Wei Yang: Albert-Ludwigs-University Freiburg
Shaobo Cong: Albert-Ludwigs-University Freiburg
Ruoyao Li: Albert-Ludwigs-University Freiburg
Jennifer Schwarz: Albert-Ludwigs-University Freiburg
Thilo Schulze: Untere Karspüle 2
Raban A. Gevelhoff: Albert-Ludwigs-University Freiburg
Xinyan Chen: Albert-Ludwigs-University Freiburg
Sara Ullrich: Albert-Ludwigs-University Freiburg
Kristina Falkenstein: Albert-Ludwigs-University Freiburg
Denis Ott: Albert-Ludwigs-University Freiburg
Pia Eixmann: Albert-Ludwigs-University Freiburg
Angelica Trentino: Albert-Ludwigs-University Freiburg
Antje Thien: Albert-Ludwigs-University Freiburg
Thierry Heidmann: University Paris-Saclay
Ekkehard Schulze: Albert-Ludwigs-University Freiburg
Bettina Warscheid: Albert-Ludwigs-University Freiburg
Ralf Baumeister: Albert-Ludwigs-University Freiburg
Wenjing Qi: Albert-Ludwigs-University Freiburg

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: Abstract Gene duplication generates gene paralogs that may undergo diverse fates during evolution, and thus serves as a potent catalyst of biological complexity. Genetic paralogs frequently share redundant functions and may also exhibit antagonistic activities by competing for common interaction partners. Here we show that the gene paralogs NRBP1 and NRBP2 oppositely regulate long interspersed nuclear element-1 (L1) retrotransposition, via influencing integrity of the L1 ribonucleoprotein complex. We demonstrate that the opposing roles of NRBP1 and NRBP2 are not results of a competitive mechanism, but rather due to targeting NRBP1 for degradation by NRBP2, probably through heterodimer formation. Moreover, our phylogenetic analysis shows that the regulatory function of NRBP2 may be acquired later during evolution, suggesting that evolutionary pressure has favored this functional fine-tuning of NRBP1. In summary, our findings not only identify NRBP1/2 as L1 regulators and implicate their involvement in human pathogenesis, but also provide a mechanistic insight into the regulatory details arising from gene duplication.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61626-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61626-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61626-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().