Article
Phosphorylation at the disordered N-end makes HuR accumulate and dimerize in the cytoplasm.
Author/s | Baños Jaime, Blanca
![]() ![]() ![]() ![]() Corrales Guerrero, Laura ![]() ![]() ![]() ![]() ![]() ![]() ![]() Pérez Mejías, Gonzalo Rejano Gordillo, Claudia M. Velázquez Campoy, Adrián Martínez Cruz, Luis Alfonso Rosa Acosta, Miguel Ángel de la ![]() ![]() ![]() ![]() ![]() ![]() Díaz Moreno, Irene ![]() ![]() ![]() ![]() ![]() ![]() ![]() |
Department | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Publication Date | 2024-07-05 |
Deposit Date | 2024-07-17 |
Published in |
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Abstract | Human antigen R (HuR) is an RNA binding protein mainly involved in maintaining the stability and controlling the translation of mRNAs, critical
for immune response, cell survival, proliferation and apoptosis. Although HuR ... Human antigen R (HuR) is an RNA binding protein mainly involved in maintaining the stability and controlling the translation of mRNAs, critical for immune response, cell survival, proliferation and apoptosis. Although HuR is a nuclear protein, its mRNA translational-related function occurs at the cytoplasm, where the oligomeric form of HuR is more abundant. However, the regulation of nucleo-cytoplasmic transport of HuR and its connection with protein oligomerization remain unclear. In this work, we describe the phosphorylation of Tyr5 as a new hallmark for HuR activation. Our biophysical, structural and computational assays using phosphorylated and phosphomimetic HuR proteins demonstrate that phosphorylation of Tyr5 at the disordered N-end stretch induces global changes on HuR dynamics and conformation, modifying the solvent accessible surface of the HuR nucleo-cytoplasmic shuttling (HNS) sequence and releasing regions implicated in HuR dimerization. These findings explain the preferential cytoplasmic accumulation of phosphorylated HuR in HeLa cells, aiding to comprehend the mechanisms underlying HuR nucleus-cytoplasm shuttling and its later dimerization, both of which are relevant in HuR-related pathogenesis. |
Funding agencies | Agencia Estatal de Investigación. España Ministerio de Ciencia e Innovación (MICIN). España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Junta de Andalucía Universidad de Sevilla Ministerio de Educación, Cultura y Deporte (MECD). España |
Citation | Baños Jaime, B., Corrales Guerrero, L., Pérez Mejías, G., Rejano Gordillo, C.M., Velázquez Campoy, A., Martínez Cruz, L.A.,...,Díaz Moreno, I. (2024). Phosphorylation at the disordered N-end makes HuR accumulate and dimerize in the cytoplasm.. Nucleic Acids Research, 2024, gkae564. https://doi.org/10.1093/nar/gkae564. |
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