Translation of Small Open Reading Frames: Roles in Regulation and Evolutionary Innovation

The translatome can be defined as the sum of the RNA sequences that are translated into proteins in the cell by the ribosomal machinery. Until recently, it was generally assumed that the translatome was essentially restricted to evolutionary conserved proteins encoded by the set of annotated protein-coding genes. However, it has become increasingly clear that it also includes small regulatory open reading frames (ORFs), functional micropeptides, de novo proteins, and the pervasive translation of likely nonfunctional proteins. Many of these ORFs have been discovered thanks to the development of ribosome profiling, a technique to sequence ribosome-protected RNA fragments. To fully capture the diversity of translated ORFs, we propose a comprehensive classification that includes the new types of translated ORFs in addition to standard proteins.