TY  - JOUR
AU  - Roiuk, Mykola
AU  - Neff, Marilena
AU  - Teleman, Aurelio
TI  - Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control in HeLa cells.
JO  - eLife
VL  - 14
SN  - 2050-084X
CY  - Cambridge
PB  - eLife Sciences Publications
M1  - DKFZ-2025-01409
SP  - RP105311
PY  - 2025
N1  - #EA:B140#LA:B140#
AB  - Translation initiation in eukaryotes requires a 40 S ribosome loaded with initiator tRNA which scans for an initiation codon. The initiator tRNA is usually recruited to the ribosome as part of a ternary complex composed of initiator tRNA, eIF2, and GTP. Although initiator tRNA recruitment was originally ascribed to another factor, eIF2A, it was later disproven and shown to occur via eIF2. Nonetheless, eIF2A is still considered a translation initiation factor because it binds the ribosome and shows genetic interactions with other initiation factors such as eIF4E. The exact function of eIF2A during translation initiation, however, remains unclear. Here, we use ribosome profiling and luciferase reporter assays to systematically test in HeLa cells the role of eIF2A in translation initiation, including translation of upstream ORFs. Since eIF2A is thought to take over the function of eIF2 when eIF2 is inhibited, we also test conditions where the integrated stress response is activated. In none of our assays, however, could we detect a role of eIF2A in translation initiation. It is possible that eIF2A plays a role in translation regulation in specific conditions that we have not tested here, or that it plays a role in a different aspect of RNA biology.
KW  - Humans
KW  - HeLa Cells
KW  - Eukaryotic Initiation Factor-2: metabolism
KW  - Eukaryotic Initiation Factor-2: genetics
KW  - Peptide Chain Initiation, Translational
KW  - Open Reading Frames
KW  - Protein Biosynthesis
KW  - Ribosomes: metabolism
KW  - biochemistry (Other)
KW  - chemical biology (Other)
KW  - developmental biology (Other)
KW  - eIF2 (Other)
KW  - eIF2A (Other)
KW  - human (Other)
KW  - translation (Other)
KW  - Eukaryotic Initiation Factor-2 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40600802
C2  - pmc:PMC12221301
DO  - DOI:10.7554/eLife.105311
UR  - https://inrepo02.dkfz.de/record/302869
ER  -