Post-Transcriptional Modifications of RNA: Impact on RNA Function and Human Health

Abstract

Epitranscriptomics is the study of global modification patterns to both coding and noncoding RNA. Understanding the epitranscriptomic profile of disease states or individual patients is imperative to understanding human health and molecular disease pathology. Modifications have long been established as important determinants of tRNA stability, dynamics, and ribosome binding and of maintenance of the translational reading frame. These modifications also serve as biomarkers for several human diseases, including type 2 diabetes, cardiac dysfunction, intellectual disability, and skin, breast, and colorectal cancers. Of particular note, several mitochondrial disorders trace their molecular pathogenesis to deficiencies in specific tRNA modifications. Pathology can also be attributed to mutations affecting protein recognition of tRNA substrates. However, protein recognition of RNA modification is at present an underdeveloped field and the subject of increasing attention. Epitranscriptomic profiling will be readily achievable with new advances in the detection of RNA modifications by peptides and mass spectrometry at the attomole level. These technologies will allow for single-cell analysis of modifications and will serve as a platform for increased sensitivity for biomarker identification. Thus, RNA modifications are a real-time code to RNA structure and function that has yet to be deciphered.