eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions
Translation initiation in eukaryotes is a multi-step pathway and the most regulated phase of translation. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex of the translation initiation factors, and it contributes to events throughout the initiation pathway. In particular, eIF3 a...
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2021.787664/full |
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| author | Andrei Stanciu Juncheng Luo Lucy Funes Shanya Galbokke Hewage Shardul D. Kulkarni Colin Echeverría Aitken Colin Echeverría Aitken |
| author_facet | Andrei Stanciu Juncheng Luo Lucy Funes Shanya Galbokke Hewage Shardul D. Kulkarni Colin Echeverría Aitken Colin Echeverría Aitken |
| author_sort | Andrei Stanciu |
| collection | DOAJ |
| description | Translation initiation in eukaryotes is a multi-step pathway and the most regulated phase of translation. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex of the translation initiation factors, and it contributes to events throughout the initiation pathway. In particular, eIF3 appears to play critical roles in mRNA recruitment. More recently, eIF3 has been implicated in driving the selective translation of specific classes of mRNAs. However, unraveling the mechanism of these diverse contributions—and disentangling the roles of the individual subunits of the eIF3 complex—remains challenging. We employed ribosome profiling of budding yeast cells expressing two distinct mutations targeting the eIF3 complex. These mutations either disrupt the entire complex or subunits positioned near the mRNA-entry channel of the ribosome and which appear to relocate during or in response to mRNA binding and start-codon recognition. Disruption of either the entire eIF3 complex or specific targeting of these subunits affects mRNAs with long 5′-untranslated regions and whose translation is more dependent on eIF4A, eIF4B, and Ded1 but less dependent on eIF4G, eIF4E, and PABP. Disruption of the entire eIF3 complex further affects mRNAs involved in mitochondrial processes and with structured 5′-untranslated regions. Comparison of the suite of mRNAs most sensitive to both mutations with those uniquely sensitive to disruption of the entire complex sheds new light on the specific roles of individual subunits of the eIF3 complex. |
| first_indexed | 2024-04-14T00:35:46Z |
| format | Article |
| id | doaj.art-611380bfa51842e1b1611cc030f9b47e |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-14T00:35:46Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-611380bfa51842e1b1611cc030f9b47e2022-12-22T02:22:23ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-01-01810.3389/fmolb.2021.787664787664eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated RegionsAndrei Stanciu0Juncheng Luo1Lucy Funes2Shanya Galbokke Hewage3Shardul D. Kulkarni4Colin Echeverría Aitken5Colin Echeverría Aitken6Computer Science Department, Vassar College, Poughkeepsie, NY, United StatesBiochemistry Program, Vassar College, Poughkeepsie, NY, United StatesBiology Department, Vassar College, Poughkeepsie, NY, United StatesBiology Department, Vassar College, Poughkeepsie, NY, United StatesDepartment of Biochemistry and Molecular Biology, Penn State Eberly College of Medicine, University Park, PA, United StatesBiochemistry Program, Vassar College, Poughkeepsie, NY, United StatesBiology Department, Vassar College, Poughkeepsie, NY, United StatesTranslation initiation in eukaryotes is a multi-step pathway and the most regulated phase of translation. Eukaryotic initiation factor 3 (eIF3) is the largest and most complex of the translation initiation factors, and it contributes to events throughout the initiation pathway. In particular, eIF3 appears to play critical roles in mRNA recruitment. More recently, eIF3 has been implicated in driving the selective translation of specific classes of mRNAs. However, unraveling the mechanism of these diverse contributions—and disentangling the roles of the individual subunits of the eIF3 complex—remains challenging. We employed ribosome profiling of budding yeast cells expressing two distinct mutations targeting the eIF3 complex. These mutations either disrupt the entire complex or subunits positioned near the mRNA-entry channel of the ribosome and which appear to relocate during or in response to mRNA binding and start-codon recognition. Disruption of either the entire eIF3 complex or specific targeting of these subunits affects mRNAs with long 5′-untranslated regions and whose translation is more dependent on eIF4A, eIF4B, and Ded1 but less dependent on eIF4G, eIF4E, and PABP. Disruption of the entire eIF3 complex further affects mRNAs involved in mitochondrial processes and with structured 5′-untranslated regions. Comparison of the suite of mRNAs most sensitive to both mutations with those uniquely sensitive to disruption of the entire complex sheds new light on the specific roles of individual subunits of the eIF3 complex.https://www.frontiersin.org/articles/10.3389/fmolb.2021.787664/fulleIF3translation initiationtranslational regulationmRNA recruitmentribosomeribosome profiling |
| spellingShingle | Andrei Stanciu Juncheng Luo Lucy Funes Shanya Galbokke Hewage Shardul D. Kulkarni Colin Echeverría Aitken Colin Echeverría Aitken eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions Frontiers in Molecular Biosciences eIF3 translation initiation translational regulation mRNA recruitment ribosome ribosome profiling |
| title | eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions |
| title_full | eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions |
| title_fullStr | eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions |
| title_full_unstemmed | eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions |
| title_short | eIF3 and Its mRNA-Entry-Channel Arm Contribute to the Recruitment of mRNAs With Long 5′-Untranslated Regions |
| title_sort | eif3 and its mrna entry channel arm contribute to the recruitment of mrnas with long 5 untranslated regions |
| topic | eIF3 translation initiation translational regulation mRNA recruitment ribosome ribosome profiling |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2021.787664/full |
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