Going global: the new era of mapping modifications in <scp>RNA</scp>

<jats:p>The post‐transcriptional modification of <jats:styled-content style="fixed-case">RNA</jats:styled-content> by the addition of one or more chemical groups has been known for over 50 years. These chemical modifications, once thought to be static, are now being discovered to play key regulatory roles in gene expression. The advent of massive parallel sequencing of <jats:styled-content style="fixed-case">RNA</jats:styled-content> (<jats:styled-content style="fixed-case">RNA</jats:styled-content>‐seq) now allows us to probe the complexity of cellular <jats:styled-content style="fixed-case">RNA</jats:styled-content> and how chemically altering <jats:styled-content style="fixed-case">RNA</jats:styled-content> structure expands the <jats:styled-content style="fixed-case">RNA</jats:styled-content> vocabulary. Here we present an overview of the various strategies and technologies that are available to profile <jats:styled-content style="fixed-case">RNA</jats:styled-content> chemical modifications at the cellular level. These strategies can be characterized as targeted and untargeted approaches: targeted strategies are developed for one single chemical modification while untargeted strategies are more broadly applicable to a range of such chemical changes. Key for all of these approaches is the ability to locate modifications within the <jats:styled-content style="fixed-case">RNA</jats:styled-content> sequence. While most of these methods are built upon an <jats:styled-content style="fixed-case">RNA</jats:styled-content>‐Seq pipeline, alternative approaches based on mass spectrometry or conventional <jats:styled-content style="fixed-case">DNA</jats:styled-content> sequencing retain value in the overall analysis process. We also look forward toward future opportunities and technologies that may expand the types of modifications that can be globally profiled. Given the ever increasing recognition that these <jats:styled-content style="fixed-case">RNA</jats:styled-content> chemical modifications play important biological roles, a variety of methods, preferably orthogonal approaches, will be required to globally identify, validate and quantify <jats:styled-content style="fixed-case">RNA</jats:styled-content> chemical modifications found in the transcriptome. <jats:italic>WIREs RNA</jats:italic> 2017, 8:e1367. doi: 10.1002/wrna.1367</jats:p><jats:p>This article is categorized under: <jats:list list-type="explicit-label"> <jats:list-item><jats:p>RNA Structure and Dynamics > RNA Structure, Dynamics, and Chemistry</jats:p></jats:list-item> <jats:list-item><jats:p>RNA Processing > RNA Editing and Modification</jats:p></jats:list-item> <jats:list-item><jats:p>RNA Methods > RNA Analyses In Vitro and In Silico</jats:p></jats:list-item> </jats:list></jats:p>