First Author | Fujii K | Year | 2021 |
Journal | Dev Cell | Volume | 56 |
Issue | 21 | Pages | 2928-2937.e9 |
PubMed ID | 34752747 | Mgi Jnum | J:314131 |
Mgi Id | MGI:6814664 | Doi | 10.1016/j.devcel.2021.10.009 |
Citation | Fujii K, et al. (2021) Controlling tissue patterning by translational regulation of signaling transcripts through the core translation factor eIF3c. Dev Cell 56(21):2928-2937.e9 |
abstractText | Although gene expression is tightly regulated during embryonic development, the impact of translational control has received less experimental attention. Here, we find that eukaryotic translation initiation factor-3 (eIF3) is required for Shh-mediated tissue patterning. Analysis of loss-of-function eIF3 subunit c (Eif3c) mice reveal a unique sensitivity to the Shh receptor patched 1 (Ptch1) dosage. Genome-wide in vivo enhanced cross-linking immunoprecipitation sequence (eCLIP-seq) shows unexpected specificity for eIF3 binding to a pyrimidine-rich motif present in subsets of 5'-UTRs and a corresponding change in the translation of these transcripts by ribosome profiling in Eif3c loss-of-function embryos. We further find a transcript specific effect in Eif3c loss-of-function embryos whereby translation of Ptch1 through this pyrimidine-rich motif is specifically sensitive to eIF3 amount. Altogether, this work uncovers hidden specificity of housekeeping translation initiation machinery for the translation of key developmental signaling transcripts. |