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| Home > Publications database > MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays. > print |
| Home > Publications database > MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays. > print |
| 001 | 296113 | ||
| 005 | 20250311145908.0 | ||
| 024 | 7 | _ | |a 10.1038/s44318-024-00347-3 |2 doi |
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| 037 | _ | _ | |a DKFZ-2025-00043 |
| 041 | _ | _ | |a English |
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| 100 | 1 | _ | |a Meurs, Romane |0 0000-0003-3115-2501 |b 0 |
| 245 | _ | _ | |a MCTS2 and distinct eIF2D roles in uORF-dependent translation regulation revealed by in vitro re-initiation assays. |
| 260 | _ | _ | |a Hoboken, NJ [u.a.] |c 2025 |b Wiley |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1741701505_25289 |2 PUB:(DE-HGF) |
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| 500 | _ | _ | |a 2025 Feb;44(3):854-876 |
| 520 | _ | _ | |a Ribosomes scanning from the mRNA 5' cap to the start codon may initiate at upstream open reading frames (uORFs), decreasing protein biosynthesis. Termination at a uORF can lead to re-initiation, where 40S subunits resume scanning and initiate another translation event downstream. The noncanonical translation factors MCTS1-DENR participate in re-initiation at specific uORFs, but knowledge of other trans-acting factors or uORF features influencing re-initiation is limited. Here, we establish a cell-free re-initiation assay using HeLa lysates to address this question. Comparing in vivo and in vitro re-initiation on uORF-containing reporters, we validate MCTS1-DENR-dependent re-initiation in vitro. Using this system and ribosome profiling in cells, we found that knockdown of the MCTS1-DENR homolog eIF2D causes widespread gene deregulation unrelated to uORF translation, and thus distinct to MCTS1-DENR-dependent re-initiation regulation. Additionally, we identified MCTS2, encoded by an Mcts1 retrogene, as a DENR partner promoting re-initiation in vitro, providing a plausible explanation for clinical differences associated with DENR vs. MCTS1 mutations in humans. |
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| 650 | _ | 7 | |a DENR-MCTS1 |2 Other |
| 650 | _ | 7 | |a In Vitro Translation |2 Other |
| 650 | _ | 7 | |a Re-Initiation |2 Other |
| 650 | _ | 7 | |a eIF2D |2 Other |
| 650 | _ | 7 | |a uORF |2 Other |
| 700 | 1 | _ | |a De Matos, Mara |b 1 |
| 700 | 1 | _ | |a Bothe, Adrian |0 0009-0007-2710-1273 |b 2 |
| 700 | 1 | _ | |a Guex, Nicolas |0 0000-0001-6023-0519 |b 3 |
| 700 | 1 | _ | |a Weber, Tobias |0 P:(DE-He78)92828afe777c83bb1efb2f2f5bbb060a |b 4 |u dkfz |
| 700 | 1 | _ | |a Teleman, Aurelio |0 P:(DE-He78)5ebc16fd8019dbfde58e0125b001b599 |b 5 |u dkfz |
| 700 | 1 | _ | |a Ban, Nenad |0 0000-0002-9527-210X |b 6 |
| 700 | 1 | _ | |a Gatfield, David |0 0000-0001-5114-2824 |b 7 |
| 773 | _ | _ | |a 10.1038/s44318-024-00347-3 |0 PERI:(DE-600)1467419-1 |n 3 |p 854-876 |t The EMBO journal |v 44 |y 2025 |x 0261-4189 |
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