Contribution of disordered regions of the essential protein GEMIN5 to RNA binding
- 1Centro de Biología Molecular Severo Ochoa (CBM), CSIC-UAM
- 2Escuela de Doctorado, Universidad Autónoma de Madrid (UAM), Madrid, Spain
Abstract
GEMIN5 is emerging as a multifunctional RNA-binding protein (RBP) linked to human disease. This RBP comprises a WD40 repeat domain at the N terminus. The C-terminal region (G5C) includes a tetratricopeptide repeat (TPR)-like dimerization module, a non-canonical RNA-binding site (RBS), and an intrinsically disordered region (IDR). Understanding the molecular basis for RNA binding is critical to decipher how GEMIN5 pathological variants impact on their functions. Here we show that the RNA-binding domain consists of an extended binding surface comprising a serine-rich loop and an acidic cluster within the IDR. The RNA binding ability measured in vitro and in soluble cellular extracts indicated that individually, ser-rich motif and acidic cluster mutants diminished RNA binding intensity. However, in the absence of the RBS region, the TPR-extended protein is sufficient to facilitate RNA binding. AlphaFold modeling of the TPR-extended protein shows the assembly of an elongated dimer bound to RNA. The same RBS is observed in the G5C–RNA oligomer model. We propose that the elongated dimer forms an extended binding surface, fine-tuning the RNA binding ability of the G5C architecture.
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BibTeX
@article{franciscovelilla2026contribution,
title = {{Contribution of disordered regions of the essential protein GEMIN5 to RNA binding}},
author = {Rosario Francisco-Velilla and Azadeh Nahavandi Araghi and Jorge Ramajo and Salvador Abellan and Encarnacion Martinez-Salas},
journal = {Life Science Alliance},
year = {2026},
month = oct,
doi = {10.26508/lsa.202603860},
url = {https://www.life-science-alliance.org/lookup/doi/10.26508/lsa.202603860},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Contribution of disordered regions of the essential protein GEMIN5 to RNA binding
AU - Rosario Francisco-Velilla
AU - Azadeh Nahavandi Araghi
AU - Jorge Ramajo
AU - Salvador Abellan
AU - Encarnacion Martinez-Salas
PY - 2026
DA - 2026/10/27
JO - Life Science Alliance
DO - 10.26508/lsa.202603860
UR - https://www.life-science-alliance.org/lookup/doi/10.26508/lsa.202603860
AB - GEMIN5 is emerging as a multifunctional RNA-binding protein (RBP) linked to human disease. This RBP comprises a WD40 repeat domain at the N terminus. The C-terminal region (G5C) includes a tetratricopeptide repeat (TPR)-like dimerization module, a non-canonical RNA-binding site (RBS), and an intrinsically disordered region (IDR). Understanding the molecular basis for RNA binding is critical to decipher how GEMIN5 pathological variants impact on their functions. Here we show that the RNA-binding domain consists of an extended binding surface comprising a serine-rich loop and an acidic cluster within the IDR. The RNA binding ability measured in vitro and in soluble cellular extracts indicated that individually, ser-rich motif and acidic cluster mutants diminished RNA binding intensity. However, in the absence of the RBS region, the TPR-extended protein is sufficient to facilitate RNA binding. AlphaFold modeling of the TPR-extended protein shows the assembly of an elongated dimer bound to RNA. The same RBS is observed in the G5C–RNA oligomer model. We propose that the elongated dimer forms an extended binding surface, fine-tuning the RNA binding ability of the G5C architecture.
SN - 2575-1077
ER -