Pseudouridine: the fifth RNA nucleotide with renewed interests

More than 100 different types of chemical modifications to RNA have been documented so far. Historically, most of these modifications were found in rRNA, tRNA and snRNA; recently, new methods aided by high-throughput sequencing have enabled identification of chemical modifications to mRNA, leading to the emerging field of 'RNA epigenetics'. One such example is pseudouridine, which has long been known as a RNA modification in abundant non-coding RNA (ncRNA) and has recently been found to be present in mRNAas well. This review first summarizes biogenesis and known functions of pseudouridine in ncRNAs. We then focus on progress in pseudouridine detection, especially the chemical-assisted, transcriptome-wide sequencing tools that revealed the dynamic nature of mRNA pseudouridylation. Such enabling tools are expected to facilitate future functional studies of pseudouridine.