Abstract
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 alternative 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.
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References
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Acknowledgements
We thank members of the Gilbert lab for helpful discussions. We thank Erin Borchardt and Kristen W Lynch for their reading of the manuscript and suggestions. Funding sources: Jane Coffin Childs Memorial Fund Fellowship to Nicole M. Martinez NIH (GM101316 and CA187236) and the American Cancer Society (RSG-13-396-01-RMC) to Wendy V. Gilbert.
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Author summary: Modified nucleotides in messenger RNA are abundant, inducible in response to cellular conditions and can affect diverse stages of the mRNA life cycle. In this article we highlight those mRNA modifications that are known or are likely to be deposited in pre-mRNA co-transcriptionally and discuss individual examples of modified nucleotides in pre-mRNA that influence splicing.
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Martinez, N.M., Gilbert, W.V. Pre-mRNA modifications and their role in nuclear processing. Quant Biol 6, 210–227 (2018). https://doi.org/10.1007/s40484-018-0147-4
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DOI: https://doi.org/10.1007/s40484-018-0147-4