000292099 001__ 292099 000292099 005__ 20250328112420.0 000292099 0247_ $$2doi$$a10.1038/s41467-024-51027-z 000292099 0247_ $$2pmid$$apmid:39107322 000292099 0247_ $$2altmetric$$aaltmetric:166279442 000292099 037__ $$aDKFZ-2024-01598 000292099 041__ $$aEnglish 000292099 082__ $$a500 000292099 1001_ $$0P:(DE-He78)4543601bf14234f35021d658a5228201$$aRoiuk, Mykola$$b0$$eFirst author$$udkfz 000292099 245__ $$aeIF4E-independent translation is largely eIF3d-dependent. 000292099 260__ $$a[London]$$bNature Publishing Group UK$$c2024 000292099 3367_ $$2DRIVER$$aarticle 000292099 3367_ $$2DataCite$$aOutput Types/Journal article 000292099 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1723036814_31772 000292099 3367_ $$2BibTeX$$aARTICLE 000292099 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000292099 3367_ $$00$$2EndNote$$aJournal Article 000292099 500__ $$a#EA:B140#LA:B140# 000292099 520__ $$aTranslation initiation is a highly regulated step needed for protein synthesis. Most cell-based mechanistic work on translation initiation has been done using non-stressed cells growing in medium with sufficient nutrients and oxygen. This has yielded our current understanding of 'canonical' translation initiation, involving recognition of the mRNA cap by eIF4E1 followed by successive recruitment of initiation factors and the ribosome. Many cells, however, such as tumor cells, are exposed to stresses such as hypoxia, low nutrients or proteotoxic stress. This leads to inactivation of mTORC1 and thereby inactivation of eIF4E1. Hence the question arises how cells translate mRNAs under such stress conditions. We study here how mRNAs are translated in an eIF4E1-independent manner by blocking eIF4E1 using a constitutively active version of eIF4E-binding protein (4E-BP). Via ribosome profiling we identify a subset of mRNAs that are still efficiently translated when eIF4E1 is inactive. We find that these mRNAs preferentially release eIF4E1 when eIF4E1 is inactive and bind instead to eIF3d via its cap-binding pocket. eIF3d then enables these mRNAs to be efficiently translated due to its cap-binding activity. In sum, our work identifies eIF3d-dependent translation as a major mechanism enabling mRNA translation in an eIF4E-independent manner. 000292099 536__ $$0G:(DE-HGF)POF4-312$$a312 - Funktionelle und strukturelle Genomforschung (POF4-312)$$cPOF4-312$$fPOF IV$$x0 000292099 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de 000292099 650_7 $$2NLM Chemicals$$aEukaryotic Initiation Factor-4E 000292099 650_7 $$2NLM Chemicals$$aEukaryotic Initiation Factor-3 000292099 650_7 $$2NLM Chemicals$$aRNA, Messenger 000292099 650_7 $$2NLM Chemicals$$aEIF3D protein, human 000292099 650_7 $$2NLM Chemicals$$aEIF4E protein, human 000292099 650_7 $$2NLM Chemicals$$aRNA Caps 000292099 650_7 $$2NLM Chemicals$$aEIF4EBP1 protein, human 000292099 650_7 $$2NLM Chemicals$$aCell Cycle Proteins 000292099 650_7 $$2NLM Chemicals$$aAdaptor Proteins, Signal Transducing 000292099 650_2 $$2MeSH$$aEukaryotic Initiation Factor-4E: metabolism 000292099 650_2 $$2MeSH$$aEukaryotic Initiation Factor-4E: genetics 000292099 650_2 $$2MeSH$$aEukaryotic Initiation Factor-3: metabolism 000292099 650_2 $$2MeSH$$aEukaryotic Initiation Factor-3: genetics 000292099 650_2 $$2MeSH$$aHumans 000292099 650_2 $$2MeSH$$aRNA, Messenger: metabolism 000292099 650_2 $$2MeSH$$aRNA, Messenger: genetics 000292099 650_2 $$2MeSH$$aProtein Biosynthesis 000292099 650_2 $$2MeSH$$aRibosomes: metabolism 000292099 650_2 $$2MeSH$$aProtein Binding 000292099 650_2 $$2MeSH$$aRNA Caps: metabolism 000292099 650_2 $$2MeSH$$aHEK293 Cells 000292099 650_2 $$2MeSH$$aPeptide Chain Initiation, Translational 000292099 650_2 $$2MeSH$$aCell Cycle Proteins 000292099 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing 000292099 7001_ $$0P:(DE-He78)725adf28bb1f2600ee6fca8c48266e56$$aNeff, Marilena$$b1$$udkfz 000292099 7001_ $$0P:(DE-He78)5ebc16fd8019dbfde58e0125b001b599$$aTeleman, Aurelio$$b2$$eLast author$$udkfz 000292099 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-51027-z$$gVol. 15, no. 1, p. 6692$$n1$$p6692$$tNature Communications$$v15$$x2041-1723$$y2024 000292099 8564_ $$uhttps://inrepo02.dkfz.de/record/292099/files/s41467-024-51027-z.pdf 000292099 8564_ $$uhttps://inrepo02.dkfz.de/record/292099/files/s41467-024-51027-z.pdf?subformat=pdfa$$xpdfa 000292099 8767_ $$8SN-2024-01444-b$$92024-12-05$$d2025-03-27$$eAPC$$jZahlung erfolgt 000292099 909CO $$ooai:inrepo02.dkfz.de:292099$$pVDB$$pOpenAPC$$popenCost 000292099 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4543601bf14234f35021d658a5228201$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ 000292099 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)725adf28bb1f2600ee6fca8c48266e56$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ 000292099 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)5ebc16fd8019dbfde58e0125b001b599$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ 000292099 9131_ $$0G:(DE-HGF)POF4-312$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vFunktionelle und strukturelle Genomforschung$$x0 000292099 9141_ $$y2024 000292099 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bNAT COMMUN : 2022$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2023-05-02T09:09:09Z 000292099 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2023-05-02T09:09:09Z 000292099 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Peer review$$d2023-05-02T09:09:09Z 000292099 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ$$d2023-05-02T09:09:09Z 000292099 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2023-08-29 000292099 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - 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