The alternative proteome in neurobiology

Translation involves the biosynthesis of a protein sequence following the decoding of the genetic information embedded in a messenger RNA (mRNA). Typically, the eukaryotic mRNA was considered to be inherently monocistronic, but this paradigm is not in agreement with the translational landscape of cells, tissues, and organs. Recent ribosome sequencing (Ribo-seq) and proteomics studies show that, in addition to currently annotated reference proteins (RefProt), other proteins termed alternative proteins (AltProts), and microproteins are encoded in regions of mRNAs thought to be untranslated or in transcripts annotated as non-coding. This experimental evidence expands the repertoire of functional proteins within a cell and potentially provides important information on biological processes. This review explores the hitherto overlooked alternative proteome in neurobiology and considers the role of AltProts in pathological and healthy neuromolecular processes.