Journal Article

New Twists in Detecting mRNA Modification Dynamics

Soller, Matthias, Janga, Sarath C., Simpson, Jared T., Mir, Quoseena, Anreiter, Ina

2021

Overview

Modified nucleotides in mRNA are an essential addition to the standard genetic code of four nucleotides in animals, plants, and their viruses. The emerging field of epitranscriptomics examines nucleotide modifications in mRNA and their impact on gene expression. The low abundance of nucleotide modifications and technical limitations, however, have hampered systematic analysis of their occurrence and functions. Selective chemical and immunological identification of modified nucleotides has revealed global candidate topology maps for many modifications in mRNA, but further technical advances to increase confidence will be necessary. Single-molecule sequencing introduced by Oxford Nanopore now promises to overcome such limitations, and we summarize current progress with a particular focus on the bioinformatic challenges of this novel sequencing technology. Writers, readers, and erasers have now been discovered for many mRNA modifications.Global topographic candidate maps have been generated for many modifications, but high error rates need to be addressed by technical improvements in detection and validation using orthogonal methods that apply rigid selection criteria.Nanopore single-molecule direct RNA sequencing is progressing towards reliable detection of modified nucleotides in mRNA.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: 2′-O-ribose methylation / Adenosine / Animals / Antibodies / bioinformatics / biotechnology / Computational Biology - trends / Editing / Gene expression / Gene mapping / Genetic code / Immune system / Immunology / Internal Medicine / m5C / m6A / m6Am / mRNA modifications / Mutation - genetics / Nanopore / nanopores / Nucleotides / Porosity / Review / RNA modification / RNA polymerase / RNA, Messenger - genetics / Sequence Analysis, RNA - trends / Topology