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001     292099
005     20250328112420.0
024 7 _ |a 10.1038/s41467-024-51027-z
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100 1 _ |a Roiuk, Mykola
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245 _ _ |a eIF4E-independent translation is largely eIF3d-dependent.
260 _ _ |a [London]
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520 _ _ |a Translation initiation is a highly regulated step needed for protein synthesis. Most cell-based mechanistic work on translation initiation has been done using non-stressed cells growing in medium with sufficient nutrients and oxygen. This has yielded our current understanding of 'canonical' translation initiation, involving recognition of the mRNA cap by eIF4E1 followed by successive recruitment of initiation factors and the ribosome. Many cells, however, such as tumor cells, are exposed to stresses such as hypoxia, low nutrients or proteotoxic stress. This leads to inactivation of mTORC1 and thereby inactivation of eIF4E1. Hence the question arises how cells translate mRNAs under such stress conditions. We study here how mRNAs are translated in an eIF4E1-independent manner by blocking eIF4E1 using a constitutively active version of eIF4E-binding protein (4E-BP). Via ribosome profiling we identify a subset of mRNAs that are still efficiently translated when eIF4E1 is inactive. We find that these mRNAs preferentially release eIF4E1 when eIF4E1 is inactive and bind instead to eIF3d via its cap-binding pocket. eIF3d then enables these mRNAs to be efficiently translated due to its cap-binding activity. In sum, our work identifies eIF3d-dependent translation as a major mechanism enabling mRNA translation in an eIF4E-independent manner.
536 _ _ |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312)
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650 _ 7 |a Eukaryotic Initiation Factor-4E
|2 NLM Chemicals
650 _ 7 |a Eukaryotic Initiation Factor-3
|2 NLM Chemicals
650 _ 7 |a RNA, Messenger
|2 NLM Chemicals
650 _ 7 |a EIF3D protein, human
|2 NLM Chemicals
650 _ 7 |a EIF4E protein, human
|2 NLM Chemicals
650 _ 7 |a RNA Caps
|2 NLM Chemicals
650 _ 7 |a EIF4EBP1 protein, human
|2 NLM Chemicals
650 _ 7 |a Cell Cycle Proteins
|2 NLM Chemicals
650 _ 7 |a Adaptor Proteins, Signal Transducing
|2 NLM Chemicals
650 _ 2 |a Eukaryotic Initiation Factor-4E: metabolism
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factor-4E: genetics
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factor-3: metabolism
|2 MeSH
650 _ 2 |a Eukaryotic Initiation Factor-3: genetics
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a RNA, Messenger: metabolism
|2 MeSH
650 _ 2 |a RNA, Messenger: genetics
|2 MeSH
650 _ 2 |a Protein Biosynthesis
|2 MeSH
650 _ 2 |a Ribosomes: metabolism
|2 MeSH
650 _ 2 |a Protein Binding
|2 MeSH
650 _ 2 |a RNA Caps: metabolism
|2 MeSH
650 _ 2 |a HEK293 Cells
|2 MeSH
650 _ 2 |a Peptide Chain Initiation, Translational
|2 MeSH
650 _ 2 |a Cell Cycle Proteins
|2 MeSH
650 _ 2 |a Adaptor Proteins, Signal Transducing
|2 MeSH
700 1 _ |a Neff, Marilena
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700 1 _ |a Teleman, Aurelio
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773 _ _ |a 10.1038/s41467-024-51027-z
|g Vol. 15, no. 1, p. 6692
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|t Nature Communications
|v 15
|y 2024
|x 2041-1723
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