Background:Cellular non-coding RNAs are extensively modified post-transcriptionally,with more than 100 chemically distinct nucleotides identified to date.In the past five years,new sequencing based methods have revealed widespread decoration of eukaryotic messenger RNA with diverse RNA modifications whose functions in mRNA metabolism are only beginning to be known.Results:Since most of the identified mRNA modifying enzymes are present in the nucleus,these modifications have the potential to function in nuclear pre-mRNA processing including alteative splicing.Here we review recent progress towards illuminating the role of pre-mRNA modifications in splicing and highlight key areas for future investigation in this rapidly growing field.Conclusions:Future studies to identify which modifications are added to nascent pre-mRNA and to interrogate the direct effects of individual modifications are likely to reveal new mechanisms by which nuclear pre-mRNA processing is regulated.