Making sense of mRNA translational “noise”

The importance of translation fidelity has been apparent since the discovery of genetic code. It is commonly believed that translation deviating from the main coding region is to be avoided at all times inside cells. However, ribosome profiling and mass spectrometry have revealed pervasive noncanonical translation. Both the scope and origin of translational “noise” are just beginning to be appreciated. Although largely overlooked, those translational “noises” are associated with a wide range of cellular functions, such as producing unannotated protein products. Furthermore, the dynamic nature of translational “noise” is responsive to stress conditions, highlighting the beneficial effect of translational “noise” in stress adaptation. Mechanistic investigation of translational “noise” will provide better insight into the mechanisms of translational regulation. Ultimately, they are not “noise” at all but represent a signature of cellular activities under pathophysiological conditions. Deciphering translational “noise” holds the therapeutic and diagnostic potential in a wide spectrum of human diseases.