How is translation regulated and specialized 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).

uORF translation is enriched in meiotic cells. Ribosome footprints are plotted over a sample gene, TRM13, showing enrichment for ribosomes in the 5' leader region (commonly called the 5'UTR) in meiosis. These uORFs (annotated in green) represent just 4 of over 10,000 uORFs that we identified to be translated in meiosis, suggesting a noncanonical mode of translation in these cells.

uORF translation is enriched in meiotic cells. Ribosome footprints are plotted over a sample gene, TRM13, showing enrichment for ribosomes in the 5' leader region (commonly called the 5'UTR) in meiosis. These uORFs (annotated in green) represent just 4 of over 10,000 uORFs that we identified to be translated in meiosis, suggesting a noncanonical mode of translation in these cells.

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. 

Probing the basis for noncanonical translation in meiotic cells. A number of factors that may be responsible for the unusual degree of dynamic translational regulation and uORF translation in meiosis are shown. We are systematically probing examples of cis- and trans- factors like those outlined here, with the goal of understanding what is special about translation (particularly translation initiation) in meiosis.

Probing the basis for noncanonical translation in meiotic cells. A number of factors that may be responsible for the unusual degree of dynamic translational regulation and uORF translation in meiosis are shown. We are systematically probing examples of cis- and trans- factors like those outlined here, with the goal of understanding what is special about translation (particularly translation initiation) in meiosis.

This project is a collaboration with Marko Jovanovic (Aviv Regev's lab).

 

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