Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity
eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the pres...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/31476 |
| _version_ | 1811200599489773568 |
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| author | Paul Yourik Colin Echeverría Aitken Fujun Zhou Neha Gupta Alan G Hinnebusch Jon R Lorsch |
| author_facet | Paul Yourik Colin Echeverría Aitken Fujun Zhou Neha Gupta Alan G Hinnebusch Jon R Lorsch |
| author_sort | Paul Yourik |
| collection | DOAJ |
| description | eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity. Structures in the 5'-UTR and 3' of the start codon synergistically inhibit mRNA recruitment in a manner relieved by eIF4A, indicating that the factor does not act solely to melt hairpins in 5'-UTRs. Our findings that eIF4A functionally interacts with the PIC and plays important roles beyond unwinding 5'-UTR structure is consistent with a recent proposal that eIF4A modulates the conformation of the 40S ribosomal subunit to promote mRNA recruitment. |
| first_indexed | 2024-04-12T02:06:15Z |
| format | Article |
| id | doaj.art-d6bf4e8e99b7475da03c1150287622c6 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:06:15Z |
| publishDate | 2017-11-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj.art-d6bf4e8e99b7475da03c1150287622c62022-12-22T03:52:31ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.31476Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexityPaul Yourik0https://orcid.org/0000-0003-0073-1623Colin Echeverría Aitken1https://orcid.org/0000-0003-2187-0614Fujun Zhou2Neha Gupta3Alan G Hinnebusch4https://orcid.org/0000-0002-1627-8395Jon R Lorsch5https://orcid.org/0000-0002-4521-4999Laboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesLaboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesLaboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesLaboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesLaboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StatesLaboratory on the Mechanism and Regulation of Protein Synthesis, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, United StateseIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity. Structures in the 5'-UTR and 3' of the start codon synergistically inhibit mRNA recruitment in a manner relieved by eIF4A, indicating that the factor does not act solely to melt hairpins in 5'-UTRs. Our findings that eIF4A functionally interacts with the PIC and plays important roles beyond unwinding 5'-UTR structure is consistent with a recent proposal that eIF4A modulates the conformation of the 40S ribosomal subunit to promote mRNA recruitment.https://elifesciences.org/articles/31476ribosomeeIF4Atranslation initiationRNA helicaseeIF4FmRNA recruitment |
| spellingShingle | Paul Yourik Colin Echeverría Aitken Fujun Zhou Neha Gupta Alan G Hinnebusch Jon R Lorsch Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity eLife ribosome eIF4A translation initiation RNA helicase eIF4F mRNA recruitment |
| title | Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity |
| title_full | Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity |
| title_fullStr | Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity |
| title_full_unstemmed | Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity |
| title_short | Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity |
| title_sort | yeast eif4a enhances recruitment of mrnas regardless of their structural complexity |
| topic | ribosome eIF4A translation initiation RNA helicase eIF4F mRNA recruitment |
| url | https://elifesciences.org/articles/31476 |
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