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Publication : Controlling tissue patterning by translational regulation of signaling transcripts through the core translation factor eIF3c.

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.
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