Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition
During embryogenesis, Hox mRNA translation is tightly regulated by a sophisticated molecular mechanism that combines two RNA regulons located in their 5’UTR. First, an internal ribosome entry site (IRES) enables cap-independent translation. The second regulon is a translation inhibitory element or T...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2021-06-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/66369 |
| _version_ | 1811180589711097856 |
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| author | Fatima Alghoul Schaeffer Laure Gilbert Eriani Franck Martin |
| author_facet | Fatima Alghoul Schaeffer Laure Gilbert Eriani Franck Martin |
| author_sort | Fatima Alghoul |
| collection | DOAJ |
| description | During embryogenesis, Hox mRNA translation is tightly regulated by a sophisticated molecular mechanism that combines two RNA regulons located in their 5’UTR. First, an internal ribosome entry site (IRES) enables cap-independent translation. The second regulon is a translation inhibitory element or TIE, which ensures concomitant cap-dependent translation inhibition. In this study, we deciphered the molecular mechanisms of mouse Hoxa3 and Hoxa11 TIEs. Both TIEs possess an upstream open reading frame (uORF) that is critical to inhibit cap-dependent translation. However, the molecular mechanisms used are different. In Hoxa3 TIE, we identify an uORF which inhibits cap-dependent translation and we show the requirement of the non-canonical initiation factor eIF2D for this process. The mode of action of Hoxa11 TIE is different, it also contains an uORF but it is a minimal uORF formed by an uAUG followed immediately by a stop codon, namely a ‘start-stop’. The ‘start-stop’ sequence is species-specific and in mice, is located upstream of a highly stable stem loop structure which stalls the 80S ribosome and thereby inhibits cap-dependent translation of Hoxa11 main ORF. |
| first_indexed | 2024-04-11T09:05:48Z |
| format | Article |
| id | doaj.art-1e091babbcc84a9788bac47db31d2610 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:05:48Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1e091babbcc84a9788bac47db31d26102022-12-22T04:32:39ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.66369Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibitionFatima Alghoul0https://orcid.org/0000-0003-1934-9483Schaeffer Laure1Gilbert Eriani2Franck Martin3https://orcid.org/0000-0001-9724-4025Institut de Biologie Moléculaire et Cellulaire, “Architecture et Réactivité de l’ARN” CNRS UPR9002, Université de Strasbourg, Strasbourg, FranceInstitut de Biologie Moléculaire et Cellulaire, “Architecture et Réactivité de l’ARN” CNRS UPR9002, Université de Strasbourg, Strasbourg, FranceInstitut de Biologie Moléculaire et Cellulaire, “Architecture et Réactivité de l’ARN” CNRS UPR9002, Université de Strasbourg, Strasbourg, FranceInstitut de Biologie Moléculaire et Cellulaire, “Architecture et Réactivité de l’ARN” CNRS UPR9002, Université de Strasbourg, Strasbourg, FranceDuring embryogenesis, Hox mRNA translation is tightly regulated by a sophisticated molecular mechanism that combines two RNA regulons located in their 5’UTR. First, an internal ribosome entry site (IRES) enables cap-independent translation. The second regulon is a translation inhibitory element or TIE, which ensures concomitant cap-dependent translation inhibition. In this study, we deciphered the molecular mechanisms of mouse Hoxa3 and Hoxa11 TIEs. Both TIEs possess an upstream open reading frame (uORF) that is critical to inhibit cap-dependent translation. However, the molecular mechanisms used are different. In Hoxa3 TIE, we identify an uORF which inhibits cap-dependent translation and we show the requirement of the non-canonical initiation factor eIF2D for this process. The mode of action of Hoxa11 TIE is different, it also contains an uORF but it is a minimal uORF formed by an uAUG followed immediately by a stop codon, namely a ‘start-stop’. The ‘start-stop’ sequence is species-specific and in mice, is located upstream of a highly stable stem loop structure which stalls the 80S ribosome and thereby inhibits cap-dependent translation of Hoxa11 main ORF.https://elifesciences.org/articles/66369humanuORFribosometranslationhox mRNATIE |
| spellingShingle | Fatima Alghoul Schaeffer Laure Gilbert Eriani Franck Martin Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition eLife human uORF ribosome translation hox mRNA TIE |
| title | Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition |
| title_full | Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition |
| title_fullStr | Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition |
| title_full_unstemmed | Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition |
| title_short | Translation inhibitory elements from Hoxa3 and Hoxa11 mRNAs use uORFs for translation inhibition |
| title_sort | translation inhibitory elements from hoxa3 and hoxa11 mrnas use uorfs for translation inhibition |
| topic | human uORF ribosome translation hox mRNA TIE |
| url | https://elifesciences.org/articles/66369 |
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