RSK1 and RSK2 modulate the translatome of glioblastoma cells in an isoform-specific and mTORC1 independent manner

Roffé, M; Nascimento, DP; Nunes, PB; Soares, LC; Alves, ADH; Hamraghani, A; Almasi, Y; Djaoud, Z; Hajj, GNM; Martins, VR; Sonenberg, N; Alain, T

Journal article

RSK1 and RSK2 modulate the translatome of glioblastoma cells in an isoform-specific and mTORC1 independent manner

Abstract:: BackgroundThe p90 ribosomal S6 kinase (RSK) family, downstream target of Ras/ERK signaling, encompasses four human isoforms (RSK1-4). Glioblastomas (GBMs) predominantly express RSK1 and RSK2, whereby RSK1 is markedly upregulated in a subset of GBMs associated with dismal prognosis and immune infiltration, while RSK2 expression is constant. RSKs were proposed as regulators of mRNA translation through the activation of mTORC1 and other factors, such as eIF4B, but nothing is known about their effect on the translatome of GBM cells.MethodsThrough the generation of RSK1 and RSK2 knockout as well as double knockout (DKO) GBM cells, we investigated RSK isoform-specific functions in cell signaling, followed by the identification of their distinct transcriptome and translatome.ResultsWe find that mTORC1 is not activated by RSK isoforms and that eIF4B phosphorylation at S422 is more potently targeted by RSK1 than mTORC1/S6K in GBM cells. Intriguingly, RSK isoforms display differential effects on translation, with RSK1 specifically sustaining translation of a subset of mRNAs upon mTORC1 inhibition. We demonstrate that RSK1 modulates expression in the translatome of mRNAs encoding proteins affecting cell cycle, DNA replication, and repair, while RSK2 impacts mitochondria-related functions. Notably, DKO cells exhibit compounded phenotypes, underscoring the existence of isoform-specific gene regulation.ConclusionsOur findings offer mechanistic insights into the role of RSK in GBMs and provide evidence for a mTORC1-independent and RSK1-dependent translation regulatory program.

Publication status:: Published

Peer review status:: Peer reviewed

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Share
Cite

Cite this record

APA Style

Roffé, M., Nascimento, D. P., Nunes, P. B., Soares, L. C., Alves, A. D. H., Hamraghani, A., Almasi, Y., Djaoud, Z., Hajj, G. N. M., Martins, V. R., Sonenberg, N., & Alain, T. (2025). RSK1 and RSK2 modulate the translatome of glioblastoma cells in an isoform-specific and mTORC1 independent manner. Neuro-Oncology Advances, 7(1), vdaf144.

MLA Style

Roffé, M, et al. “RSK1 And RSK2 Modulate the Translatome of Glioblastoma Cells in an Isoform-Specific and mTORC1 Independent Manner.” Neuro-Oncology Advances, vol. 7, no. 1, 2025, p. vdaf144.

Chicago Style

Roffé, M, DP Nascimento, PB Nunes, et al. 2025. “RSK1 And RSK2 Modulate the Translatome of Glioblastoma Cells in an Isoform-Specific and mTORC1 Independent Manner.” Neuro-Oncology Advances 7 (1): vdaf144.
Print