Oligomerization regulates the interaction of Gemin5 with members of the SMN complex and the translation machinery.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
28 Jun 2024
28 Jun 2024
Historique:
received:
30
01
2024
accepted:
04
06
2024
revised:
29
05
2024
medline:
29
6
2024
pubmed:
29
6
2024
entrez:
28
6
2024
Statut:
epublish
Résumé
RNA-binding proteins are multifunctional molecules impacting on multiple steps of gene regulation. Gemin5 was initially identified as a member of the survival of motor neurons (SMN) complex. The protein is organized in structural and functional domains, including a WD40 repeats domain at the N-terminal region, a tetratricopeptide repeat (TPR) dimerization module at the central region, and a non-canonical RNA-binding site at the C-terminal end. The TPR module allows the recruitment of the endogenous Gemin5 protein in living cells and the assembly of a dimer in vitro. However, the biological relevance of Gemin5 oligomerization is not known. Here we interrogated the Gemin5 interactome focusing on oligomerization-dependent or independent regions. We show that the interactors associated with oligomerization-proficient domains were primarily annotated to ribosome, splicing, translation regulation, SMN complex, and RNA stability. The presence of distinct Gemin5 protein regions in polysomes highlighted differences in translation regulation based on their oligomerization capacity. Furthermore, the association with native ribosomes and negative regulation of translation was strictly dependent on both the WD40 repeats domain and the TPR dimerization moiety, while binding with the majority of the interacting proteins, including SMN, Gemin2, and Gemin4, was determined by the dimerization module. The loss of oligomerization did not perturb the predominant cytoplasmic localization of Gemin5, reinforcing the cytoplasmic functions of this essential protein. Our work highlights a distinctive role of the Gemin5 domains for its functions in the interaction with members of the SMN complex, ribosome association, and RBP interactome.
Identifiants
pubmed: 38942768
doi: 10.1038/s41420-024-02057-5
pii: 10.1038/s41420-024-02057-5
doi:
Types de publication
Journal Article
Langues
eng
Pagination
306Subventions
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PID2020-115096RB-I00
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PID2020-115096RB-I00
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PID2020-115096RB-I00
Organisme : Ministerio de Economía y Competitividad (Ministry of Economy and Competitiveness)
ID : PID2020-115096RB-I00
Informations de copyright
© 2024. The Author(s).
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