Pre-mRNA modifications and their role in nuclear processing

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.

Graphical abstract

Keywords

mRNA modification / pre-mRNA modification / splicing / RNA-modifying enzymes

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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.

COMPLIANCE WITH ETHICS GUIDELINES

The authors Nicole M. Martinez and Wendy V. Gilbert declare that they have no conflict of interests.ƒThis article is a review article and does not contain any studies with human or animal subjects performed by any of the authors.

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