Mining for Micropeptides

Abstract

Advances in computational biology and large-scale transcriptome analyses have revealed that a much larger portion of the genome is transcribed than was previously recognized, resulting in the production of a diverse population of RNA molecules with both protein-coding and non-coding potential. Emerging evidence indicates that a number of RNA molecules have been mis-annotated as non-coding and actually harbor short open reading frames (sORFs) that code for functional peptides, which have evaded detection until now due to their small size. sORF encoded peptides, or micropeptides, have been shown to play important roles in fundamental biological processes and in the maintenance of cellular homeostasis. These small proteins can act independently, for example as ligands or signaling molecules, or they can exert their biological functions by engaging with and modulating larger regulatory proteins. Given their small size, micropeptides may be uniquely suited to fine-tune complex biological systems.

A Case Study on the Keap1 Interaction with Peptide Sequence Epitopes Selected by the Peptidomic mRNA Display

“…The sequences not found in the database (N/A, 14 %) may also code peptides, because they may include unknown transcript variants . In addition, noncoding RNA (ncRNA) might include the sequences of micropeptides translated from some long ncRNA . The cDNA library was transcribed to the mRNA library by transcription and then a puromycin linker was ligated to carry out the peptidomic mRNA display.…”

MOTS‐c: A Mitochondrial‐Encoded Regulator of the Nucleus

“…Nonetheless, targeted mtDNA mutagenesis will prove to be an invaluable genetic tool to further explore not only the role of MDPs, but also a wide range of mitochondrial pathophysiology. Further, peptidomic advances will greatly aid in the analysis of known MDPs and the identification of additional peptides …”

“…Further, peptidomic advances will greatly aid in the analysis of known MDPs and the identification of additional peptides. [93,94] The role of MDPs in regulating diverse cellular and organismal functions has just begun to unravel and the field is in its infancy.…”

Using the sORFs.Org Database

“…Various tools and metrics have been developed to predict and assess the coding potential of sORFs based on RIBO‐seq and genomic information, each with their own strengths and weaknesses and applied to a certain region of interest (Makarewich & Olson, ). At sORFs.org (Olexiouk et al., , ) we predict sORFs from publicly available RIBO‐seq datasets using a lenient prediction algorithm.…”

“…The field of sORFs remains largely unexplored. Identification of sORFs is complicated by several factors: genome complexity (genome annotation, overlap with protein-coding genes, splice sites), their exclusion from searchable databases in proteomic experiments, and Various tools and metrics have been developed to predict and assess the coding potential of sORFs based on RIBO-seq and genomic information, each with their own strengths and weaknesses and applied to a certain region of interest (Makarewich & Olson, 2017). At sORFs.org (Olexiouk et al, 2015 we predict sORFs from publicly available RIBO-seq datasets using a lenient prediction algorithm.…”