How is translation regulated in meiosis?
Our original study of new protein synthesis in meiosis showed that translational regulation contributes strongly to temporal tuning of gene expression through meiosis, with 24% of genes subject to strong translational control during meiotic progression. This dataset provides a valuable tool to probe the molecular basis for, and cellular importance of, such dynamic control and the identification of the cis- and trans-factors responsible. We are currently investigating several examples of such factors, including prominently the translation of upstream Open Reading Frames (uORFs).
Thousands of instances of uORF translation were observed in cells undergoing meiosis, suggesting a meiotic shift in translation mechanism for at least a subset of transcripts. Additionally, many of these uORFs initiate translation at near-cognate (non-AUG) codons. The uORFs observed are highly discrete, specific, and heavily enriched in meiosis relative to any other condition examined to date, but the molecular basis for their translation remains a mystery. We aim to unravel both the biological significance of these uORFs as well as the translation specializations that produce them in a meiosis-specific manner.