Mining for Micropeptides

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 noncoding potential. Emerging evidence indicates that several RNA molecules have been mis-annotated as noncoding and in fact harbor short open reading frames (sORFs) that encode functional peptides and that have evaded detection until now due to their small size. sORF-encoded peptides (SEPs), or micropeptides, have been shown to have 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. Recent advances in computational and experimental techniques have revealed that a much larger portion of the genome is translated than was previously recognized. sORFs that encode functional, evolutionarily conserved peptides have been found hidden within transcripts annotated as ‘non-coding’. It has been demonstrated that these sORF-encoded peptides, or SEPs, have essential roles in many important biological processes and have been shown to act independently or as regulators of larger proteins. To date, biological roles have been assigned to a small fraction of the total putative SEPs that have been identified and a huge amount of work remains to be done to prove their existence and elucidate their functions.