eIF3 engages with 3’-UTR termini of highly translated mRNAs
Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryoti...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2025-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/102977 |
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| author | Santi Mestre-Fos Lucas Ferguson Marena I Trinidad Nicholas T Ingolia Jamie HD Cate |
| author_facet | Santi Mestre-Fos Lucas Ferguson Marena I Trinidad Nicholas T Ingolia Jamie HD Cate |
| author_sort | Santi Mestre-Fos |
| collection | DOAJ |
| description | Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs). Using Quick-irCLIP and alternative polyadenylation (APA) Seq, we show eIF3 crosslinks predominantly with 3’ untranslated region (3’-UTR) termini of multiple mRNA isoforms, adjacent to the poly(A) tail. Furthermore, we find that eIF3 engagement at 3’-UTR ends is dependent on polyadenylation. High eIF3 crosslinking at 3’-UTR termini of mRNAs correlates with high translational activity, as determined by ribosome profiling, but not with translational efficiency. The results presented here show that eIF3 engages with 3’-UTR termini of highly translated mRNAs, likely reflecting a general rather than specific regulatory function of eIF3, and supporting a role of mRNA circularization in the mechanisms governing mRNA translation. |
| format | Article |
| id | doaj-art-72f0ba5718e745e6b85da21b0330c6b5 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-72f0ba5718e745e6b85da21b0330c6b52025-01-29T17:01:13ZengeLife Sciences Publications LtdeLife2050-084X2025-01-011310.7554/eLife.102977eIF3 engages with 3’-UTR termini of highly translated mRNAsSanti Mestre-Fos0https://orcid.org/0000-0002-1355-2344Lucas Ferguson1Marena I Trinidad2Nicholas T Ingolia3https://orcid.org/0000-0002-3395-1545Jamie HD Cate4https://orcid.org/0000-0001-5965-7902Innovative Genomics Institute, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Center for Computational Biology, University of California, Berkeley, Berkeley, United StatesInnovative Genomics Institute, University of California, Berkeley, Berkeley, United States; Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, United StatesInnovative Genomics Institute, University of California, Berkeley, Berkeley, United States; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States; Department of Chemistry, University of California, Berkeley, Berkeley, United StatesStem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs). Using Quick-irCLIP and alternative polyadenylation (APA) Seq, we show eIF3 crosslinks predominantly with 3’ untranslated region (3’-UTR) termini of multiple mRNA isoforms, adjacent to the poly(A) tail. Furthermore, we find that eIF3 engagement at 3’-UTR ends is dependent on polyadenylation. High eIF3 crosslinking at 3’-UTR termini of mRNAs correlates with high translational activity, as determined by ribosome profiling, but not with translational efficiency. The results presented here show that eIF3 engages with 3’-UTR termini of highly translated mRNAs, likely reflecting a general rather than specific regulatory function of eIF3, and supporting a role of mRNA circularization in the mechanisms governing mRNA translation.https://elifesciences.org/articles/102977eIF3protein synthesis3'-UTRquick-irCLIPribosome profiling |
| spellingShingle | Santi Mestre-Fos Lucas Ferguson Marena I Trinidad Nicholas T Ingolia Jamie HD Cate eIF3 engages with 3’-UTR termini of highly translated mRNAs eLife eIF3 protein synthesis 3'-UTR quick-irCLIP ribosome profiling |
| title | eIF3 engages with 3’-UTR termini of highly translated mRNAs |
| title_full | eIF3 engages with 3’-UTR termini of highly translated mRNAs |
| title_fullStr | eIF3 engages with 3’-UTR termini of highly translated mRNAs |
| title_full_unstemmed | eIF3 engages with 3’-UTR termini of highly translated mRNAs |
| title_short | eIF3 engages with 3’-UTR termini of highly translated mRNAs |
| title_sort | eif3 engages with 3 utr termini of highly translated mrnas |
| topic | eIF3 protein synthesis 3'-UTR quick-irCLIP ribosome profiling |
| url | https://elifesciences.org/articles/102977 |
| work_keys_str_mv | AT santimestrefos eif3engageswith3utrterminiofhighlytranslatedmrnas AT lucasferguson eif3engageswith3utrterminiofhighlytranslatedmrnas AT marenaitrinidad eif3engageswith3utrterminiofhighlytranslatedmrnas AT nicholastingolia eif3engageswith3utrterminiofhighlytranslatedmrnas AT jamiehdcate eif3engageswith3utrterminiofhighlytranslatedmrnas |