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Impact of Gemin5 in protein synthesis: phosphoresidues of the dimerization domain regulate ribosome binding

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Bibliographic Details
Title: Impact of Gemin5 in protein synthesis: phosphoresidues of the dimerization domain regulate ribosome binding
Authors: Salvador Abellan, Alejandra Escos, Rosario Francisco-Velilla, Encarnacion Martinez-Salas
Source: RNA Biology, Vol 22, Iss 1, Pp 1-15 (2025)
Publisher Information: Informa UK Limited, 2025.
Publication Year: 2025
Subject Terms: translation control, phosphorylation, Genetics, ribosome binding, Gemin5, QH426-470, RNA-binding
Description: RNA-binding proteins are involved in all steps of gene expression. Their malfunction has important consequences for cell growth through dysregulation of protein synthesis events leading to cancer. Gemin5 is a predominantly cytoplasmic protein involved in spliceosome assembly and gene expression reprogramming. The protein is phosphorylated at multiple sites, although the role of the individual phosphorylated residues remains poorly understood. With the aim to understand the impact of Gemin5 post-translation modifications for RNA-binding, protein synthesis, and therefore cell growth, we have analysed the role of conserved P-residues located in the dimerization domain of the protein in subcellular localization, protein stability, interactome, ribosome binding and translation regulation. We show that the activation of signalling pathways in response to a dsRNA mimic, which leads to phosphorylation of eIF2α, enhanced the intensity of Gemin5 binding to a cognate RNA ligand. In addition, ribosome binding decreased when Ser/Thr 847 and 852–854 are substituted by a non-phosphorylatable residue, consistent with decreased protein stability, and reduced number of associated factors. Similar analyses of phosphomimetic mutants (S847D and STS852-854DDD) suggested conformational changes of the protein structure as the responsible factor for the defective proteins. Moreover, cap-dependent protein synthesis was significantly altered by the triple substitution STS/DDD, pointing towards a role of these residues in protein synthesis regulation.
Document Type: Article
Language: English
ISSN: 1555-8584
1547-6286
DOI: 10.1080/15476286.2025.2540654
Access URL: https://doaj.org/article/3a89f7ee7e65491b9e8d341ae9fe1b3d
Rights: CC BY
Accession Number: edsair.doi.dedup.....73249b9b7da9b4e94a9f4588c4c9f24c
Database: OpenAIRE
Description
Abstract:RNA-binding proteins are involved in all steps of gene expression. Their malfunction has important consequences for cell growth through dysregulation of protein synthesis events leading to cancer. Gemin5 is a predominantly cytoplasmic protein involved in spliceosome assembly and gene expression reprogramming. The protein is phosphorylated at multiple sites, although the role of the individual phosphorylated residues remains poorly understood. With the aim to understand the impact of Gemin5 post-translation modifications for RNA-binding, protein synthesis, and therefore cell growth, we have analysed the role of conserved P-residues located in the dimerization domain of the protein in subcellular localization, protein stability, interactome, ribosome binding and translation regulation. We show that the activation of signalling pathways in response to a dsRNA mimic, which leads to phosphorylation of eIF2α, enhanced the intensity of Gemin5 binding to a cognate RNA ligand. In addition, ribosome binding decreased when Ser/Thr 847 and 852–854 are substituted by a non-phosphorylatable residue, consistent with decreased protein stability, and reduced number of associated factors. Similar analyses of phosphomimetic mutants (S847D and STS852-854DDD) suggested conformational changes of the protein structure as the responsible factor for the defective proteins. Moreover, cap-dependent protein synthesis was significantly altered by the triple substitution STS/DDD, pointing towards a role of these residues in protein synthesis regulation.
ISSN:15558584
15476286
DOI:10.1080/15476286.2025.2540654