The Long History of the Diverse Roles of Short ORFs: sPEPs in Fungi

Abstract

Since the completion of the genome sequence of the model eukaryote Saccharomyces cerevisiae, there have been significant advancements in the field of genome annotation, in no small part due to the availability of datasets that make large-scale comparative analyses possible. As a result, since its completion there has been a significant change in annotated ORF size distribution in this first eukaryotic genome, especially in short ORFs (sORFs) predicted to encode polypeptides less than 150 amino acids in length. Due to their small size and the difficulties associated with their study, it is only relatively recently that these genomic features and the sORF-encoded peptides (sPEPs) they encode have become a focus of many researchers. Yet while this class of peptides may seem new and exciting, the study of this part of the proteome is nothing new in S. cerevisiae, a species where the biological importance of sPEPs has been elegantly illustrated over the past 30 years. Here the authors showcase a range of different sORFs found in S. cerevisiae and the diverse biological roles of their encoded sPEPs, and provide an insight into the sORFs found in other fungal species, particularly those pathogenic to humans.

Construction of High-Quality Rice Ribosome Footprint Library

“…Small ORFs (sORFs) are ORFs equal to or smaller than 300 nt (100 amino acids) and have been ignored for a long term because of limitations in annotation methodology (Chugunova et al, 2018). Recently ribo-seq provided evidences for genome-wide existence of sORFs in fungi (Erpf and Fraser, 2018), animals FIGURE 8 | Identification of overrepresented gene ontology (GO) terms for the discordantly expressed genes at transcription and translation levels in seedling shoots of "Nopponbare" (NB) under salt stress. The cutoff value for the overrepresented GO terms is FDR <= 0.05.…”

Short Open Reading Frames and Their Encoded Peptides

“…The minimum boundary for a bona fide protein‐coding ORF was initially set to 100 codons for gene prediction in genome annotation efforts, largely for pragmatic reasons. This arbitrary threshold has since been broadly adopted by the sORF community for the upper limit of a sPEP, although some have argued for it to be increased to 150 triplets as is the case for the Saccharomyces cerevisiae annotation . Consequently, the maximum sORF length is still being debated, ranging between 100 and 150 triplets or even larger.…”

“…Advances in methodologies to identify these hidden sORFs in the plant genomes are also highlighted in this review. Erpf and Fraser examine the fungi literature for early evidence of sORF‐encoded peptides . Remarkably, they find that the earliest report of an sPEP in these organisms is over three decades ago.…”

Ribosomal Peptides and Small Proteins on the Rise

“…One indicator of the growth and activity in this research field is the heterogeneous nomenclature for these ORFs and their products within a given cell: they are variously named short/small ORFs (sORF/smORFs), micro ORFs (miORFs), upstream ORFs (uORFs), short‐/small‐ORF‐encoded peptides (SEPs, sPEPs), short proteins, small peptides, microproteins (miPs), miniproteins, small proteins, small cellular proteome and micro proteome (Scheme ) . Adding to the confusion, one also has to take into account the arbitrarily set boundary used to distinguish between peptides and proteins at a size of 50 aa residues, despite the fact that commonly a cut‐off of 100 amino acid residues is applied .…”