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The regulation of the transcriptome is key to cellular processes that underpin cell biology, development and tissue function. All classes of cellular RNA are subject to posttranscriptional modification, be it by direct chemical modification, editing or non-templated nucleotide additions. Furthermore regulatory RNA binding proteins and enzymes that can specifically recognize posttranscriptional RNA modifications have been identified. It is now emerging that the modification status of the transcriptome is dynamic and responsive to environmental/developmental cues. Together, this has elicited the realization of an ‘epitranscriptome’ where posttranscriptional RNA modification coupled with recruitment of effector RNA binding proteins dynamically regulates genomic output and RNA function. Importantly, mutations in core-regulators of the epitranscriptome are causative in many human diseases or congenital disorders.