Controlling tissue patterning by translational regulation of signaling transcripts through the core translation...

Area of Science:

• Developmental Biology
• Molecular Biology
• Gene Regulation

Background:

• Gene expression is tightly controlled during embryonic development.
• The role of translational control, particularly by eukaryotic translation initiation factor-3 (eIF3), in development is under-explored.
• Sonic hedgehog (Shh) signaling is vital for tissue patterning.

Purpose of the Study:

• To investigate the role of eIF3 in Shh-mediated embryonic tissue patterning.
• To identify specific transcripts regulated by eIF3 during development.
• To understand the mechanism by which eIF3 influences translation of key developmental genes.

Main Methods:

• Analysis of loss-of-function Eif3c mouse models.
• Genome-wide in vivo enhanced cross-linking immunoprecipitation sequencing (eCLIP-seq) to identify eIF3 binding sites.
• Ribosome profiling to assess translational changes in Eif3c loss-of-function embryos.

Main Results:

• eIF3 is essential for Shh-mediated tissue patterning.
• eIF3 exhibits specificity for pyrimidine-rich motifs in 5'-UTRs of specific transcripts.
• Loss of Eif3c specifically impairs the translation of the Shh receptor Ptch1 via this motif, affecting its dosage sensitivity.

Conclusions:

• Housekeeping translation machinery, specifically eIF3, displays hidden specificity for regulating key developmental signaling transcripts.
• eIF3 plays a critical, previously unappreciated role in embryonic development through precise translational control.
• The findings highlight a novel layer of gene regulation critical for developmental processes.