Small Open Reading Frames

Open Reading Frames (ORFs) are the DNA sequences in the genome that has the potential to be translated. Generally, only long ORFs (≥ 300 nucleotides or nt) are thought to be protein coding regions and are considered as genes in the genome annotation pipeline. Until recent years, small ORFs (smORFs) of less than 100 codons (< 300 nt) were regarded as non-functional on the basis of empirical observations. However, recent work on ribosome profiling and mass spectrometry have led to the discovery of many translating functional small ORFs and presence of their stable peptide products. Further, examples of biologically active peptides with vital regulatory functions underline the importance of smORFs in cell functions. Genome-wide analysis shows that smORFs are conserved across diverse species, and the functional characterization of their peptides reveals their critical role in a broad spectrum of regulatory mechanisms. Further analysis of small ORFs is likely throw light on many exciting, unexplored regulatory mechanisms in different developmental stages and tissue types.