0600233 - MBÚ 2025 RIV GB eng J - Journal Article
Herrmannová, Anna - Jelínek, Jan - Pospíšilová, Klára - Kerenyi, Farkas - Vomastek, Tomáš - Watt, K. - Brábek, J. - Mohammad, Mahabub Pasha - Wagner, Susan - Topisirovic, I. - Valášek, Leoš Shivaya
Perturbations in eIF3 subunit stoichiometry alter expression of ribosomal proteins and key components of the MAPK signaling pathways.
eLife. Roč. 2024, č. 13 (2024), č. článku 95846. ISSN 2050-084X. E-ISSN 2050-084X
R&D Projects: GA ČR(CZ) GX19-25821X; GA MŠMT(CZ) EH22_008/0004575; GA ČR(CZ) GA19-08013S; GA MŠMT(CZ) LM2023055; GA MŠMT LX22NPO5102
Grant - others:AV ČR(CZ) Premium Academiae of the Academy of Sciences of the Czech Republic
Program: Akademická prémie - Praemium Academiae
Institutional support: RVO:61388971
Keywords : translation initiation * 40S subunit * eIF3 * mapk * ribosomal protein * differential expression * ribosome profiling
OECD category: Cell biology
Impact factor: 6.4, year: 2023 ; AIS: 3.675, rok: 2023
Method of publishing: Open access
Result website:
https://elifesciences.org/articles/95846DOI: https://doi.org/https://doi.org/10.7554/eLife.95846

Protein synthesis plays a major role in homeostasis and when dysregulated leads to various pathologies including cancer. To this end, imbalanced expression of eukaryotic translation initiation factors (eIFs) is not only a consequence but also a driver of neoplastic growth. eIF3 is the largest, multi-subunit translation initiation complex with a modular assembly, where aberrant expression of one subunit generates only partially functional subcomplexes. To comprehensively study the effects of eIF3 remodeling, we contrasted the impact of eIF3d, eIF3e or eIF3h depletion on the translatome of HeLa cells using Ribo-seq. Depletion of eIF3d or eIF3e, but not eIF3h reduced the levels of multiple components of the MAPK signaling pathways. Surprisingly, however, depletion of all three eIF3 subunits increased MAPK pathway activity. Depletion of eIF3e and partially eIF3d also increased translation of TOP mRNAs that encode mainly ribosomal proteins and other components of the translational machinery. Moreover, alterations in eIF3 subunit stoichiometry were often associated with changes in translation of mRNAs containing short uORFs, as in the case of the proto-oncogene MDM2 and the transcription factor ATF4. Collectively, perturbations in eIF3 subunit stoichiometry exert specific effect on the translatome comprising signaling and stress-related transcripts with complex 5' UTRs that are implicated in homeostatic adaptation to stress and cancer.
Permanent Link: https://hdl.handle.net/11104/0357586


Research data: GEO Database