Abstract
The universal expression of various non-coding RNAs (ncRNAs) is now considered the main feature of organisms' genomes. Many regions in the genome are transcribed but not annotated to encode proteins, yet contain small open reading frames (smORFs). A widely accepted opinion is that a vast majority of ncRNAs are not further translated. However, increasing evidence underlines a series of intriguing translational events from the ncRNAs, which were previously considered to lack coding potential. Recent studies also suggest that products derived from such novel translational events display important regulatory functions in many fundamental biological and pathological processes. Here we give a critical review on the potential coding capacity of ncRNAs, in particular, about what is known and unknown in this emerging area. We also discuss the possible underlying coding mechanisms of these extraordinary ncRNAs and possible roles of peptides or proteins derived from the ncRNAs in disease development and theranostics. Our review offers an extensive resource for studying the biology of ncRNAs and sheds light into the use of ncRNAs and their corresponding peptides or proteins for disease diagnosis and therapy.