Intron retention-dependent gene regulation in Cryptococcus neoformans.

Sara Gonzalez-Hilarion,Pierre Lechat,Caroline Proux,Damien Paulet,Chung-Chau Hon,Frédérique Moyrand,Estelle Mogensen,Yong-Sun Bahn,Kyung-Tae Lee,Guilhem Janbon,Jungwook Hwang,Giovanni Bussotti,Rony Barboux,Jean-Yves Coppée

doi:10.1038/srep32252

Abstract

The biological impact of alternative splicing is poorly understood in fungi, although recent studies have shown that these microorganisms are usually intron-rich. In this study, we re-annotated the genome of C. neoformans var. neoformans using RNA-Seq data. Comparison with C. neoformans var. grubii revealed that more than 99% of ORF-introns are in the same exact position in the two varieties whereas UTR-introns are much less evolutionary conserved. We also confirmed that alternative splicing is very common in C. neoformans, affecting nearly all expressed genes. We also observed specific regulation of alternative splicing by environmental cues in this yeast. However, alternative splicing does not appear to be an efficient method to diversify the C. neoformans proteome. Instead, our data suggest the existence of an intron retention-dependent mechanism of gene expression regulation that is not dependent on NMD. This regulatory process represents an additional layer of gene expression regulation in fungi and provides a mechanism to tune gene expression levels in response to any environmental modification.

Highlights

The biological impact of alternative splicing is poorly understood in fungi, recent studies have shown that these microorganisms are usually intron-rich
It is a reasonable strategy to obtain a first draft of a genome annotation, our previous re-annotation of the C. neoformans var. grubii genome revealled that intron and exon positions are very difficult to predict bioinformatically and that a large proportion of the predicted protein sequences might be wrong when no transcriptomic data is available[10]
We observed that alternative splicing is common in C. neoformans var. neoformans and that intron retention (IR) represents its most common manifestation, confirming previous reports in C. neoformans var. grubii and other fungi[10,21]

Summary

Introduction

The biological impact of alternative splicing is poorly understood in fungi, recent studies have shown that these microorganisms are usually intron-rich. The biological impact of alternative splicing has been poorly studied in part because most research has been done in Saccharomyces cerevisiae, an organism with very few introns (

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Conclusion