short Open Reading Frames (sORFs) in meiosis
Our work has uncovered surprising complexity to genome coding in meiotic yeast cells, including the translation of thousands of discrete regions between AUG codons and stop codons that were not previously thought to house genes. We systematically annotated these regions through a sensitive, empirical strategy that defined many novel Open Reading Frames (ORFs) on stable transcripts as well as alternate short isoforms of well characterized proteins, As nearly all of the new ORFs are short (sORFs), they have been excluded from traditional approaches requiring 80-100 amino acids for annotation, and cellular roles thus remain unexplored. Recent studies in diverse organisms have identified cellular functions for short peptides (for example Kondo et al., Science, 2010; Magny et al., Science, 2013), although the function of the thousands of meiotic sORFs remains a mystery. The presence of the corresponding short peptide products specifically in meiotic cells can be verified by classical methods and these early studies suggest diverse function and a rich pool of factors for functional discovery. We are investigating the significance of the meiotic enrichment of these many sORF products, as well as the individual roles of specific short peptides.
Hierarchical clustering of ribosome footprint density over the ~2500 short ORFs that we identified as translated in meiosis. Most of these are meiosis specific and highly regulated. The inset Western blot shows that the expression of these sORFs can be confirmed by classical methods.