Deciphering RNA Methylation in Cancer

Every single RNA nucleotide may undergo a variety of (post-)transcriptional chemical modifications. Historically, the inefficiency of detection methods and the difficulties in chemical structure elucidation have been a rate-limiting step in the discovery and functional analysis of ribonucleotide modifications. The current substantial progress in RNA modification profiling techniques launched epitranscriptomics as a new research field investigating this additional layer of information influencing cell physiology and disease development. RNA methylation is one of the most common and versatile chemical alterations found in the epitranscriptome, indicating a previously invisible code outside DNA and RNA sequences. Herein, we portray the historical evolution of strategies commonly used for overall and site-specific detection of methylated nucleotides in RNA and provide an overview of the relevance of these approaches for cancer biology research. We also discuss the potential of third-generation sequencing methods for direct detection of RNA methylation and prospects of RNA methylation for anticancer therapy.