Conservation and regulation of alternative splicing by dynamic inter- and intra-intron base pairings in Lepidoptera 14-3-3z pre-mRNAs

Yang, Yun; Sun, Feng; Wang, Xuebin; Yue, Yuan; Wang, Wenfeng; Zhang, Wenjing; Zhan, Leilei; Tian, Nan; Shi, Feng; Jin, Yongfeng

doi:10.4161/rna.20205

Cited by 10 publications

(13 citation statements)

References 44 publications

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“…Surprisingly, the majority of the annotated MXEs are of this type (91 of 122; 75%) as well as many exons previously annotated as other splice types (44 of 662), but only few of the novel MXEs predicted in intronic regions (25 of 615; Appendix Fig S3A and D). These numbers suggest that splicing of the remaining 484 MXE clusters is tightly regulated by other mechanisms (Fig 2B) such as RNA–protein interactions, interactions between small nuclear ribonucleoproteins and splicing factors (Lee & Rio, 2015), and competitive RNA secondary structural elements (Graveley, 2005; Yang et al , 2012; Lee & Rio, 2015). Competing RNA secondary structures are, however, usually not conserved across long evolutionary distances.…”

Section: Resultsmentioning

confidence: 99%

The landscape of human mutually exclusive splicing

Hatje

Rahman

Vidal

et al. 2017

Molecular Systems Biology

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Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA‐Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi‐cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila. Finally, MXEs are significantly enriched in pathogenic mutations and their spatio‐temporal expression might predict human disease pathology.

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Section: Resultsmentioning

confidence: 99%

The landscape of human mutually exclusive splicing

Hatje

Rahman

Vidal

et al. 2017

Molecular Systems Biology

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“…This mechanism has been shown to occur in mammalian alpha‐tropomyosin (Smith & Nadal‐Ginard, ) and insect Dscam exon 17 (Yue et al, ). Analogously, steric hindrance caused by RNA secondary structures may inhibit double exon inclusion (Yang et al, ). These models of steric interference may also explain some instances of mutually exclusive splicing of two MXEs, but not of more than two MXEs.…”

Section: Different Mechanisms Underlying Mutually Exclusive Splicingmentioning

confidence: 99%

Mutually exclusive alternative splicing of pre‐mRNAs

et al. 2018

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Pre-mRNA alternative splicing is an important mechanism used to expand protein diversity in higher eukaryotes, and mutually exclusive splicing is a specific type of alternative splicing in which only one of the exons in a cluster is included in functional transcripts. The most extraordinary example of this is the Drosophila melanogaster Down's syndrome cell adhesion molecule gene (Dscam), which potentially encodes 38,016 different isoforms through mutually exclusive splicing. Mutually exclusive splicing is a unique and challenging model that can be used to elucidate the evolution, regulatory mechanism, and function of alternative splicing. The use of new approaches has not only greatly expanded the mutually exclusive exome, but has also enabled the systematic analyses of single-cell alternative splicing during development. Furthermore, the identification of long-range RNA secondary structures provides a mechanistic framework for the regulation of mutually exclusive splicing (i.e., Dscam splicing). This article reviews recent insights into the identification, underlying mechanism, and roles of mutually exclusive splicing. This article is categorized under: RNA Processing > Splicing Regulation/Alternative Splicing RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems.

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“…2B, Supplementary Figs. S3A, S3D) such as RNA-protein interactions, interactions between small nuclear ribonucleoproteins and splicing factors (Lee & Rio, 2015), and competitive RNA secondary structural elements (Graveley, 2005;Yang et al, 2012;Suyama, 2013;Lee & Rio, 2015) ( Supplementary Fig. S18).…”

Section: Mutually Exclusive Splicing Is Tightly Regulated At the Rna mentioning

confidence: 99%

The landscape of human mutually exclusive splicing

Hatje

Vidal

Rahman

et al. 2017

Preprint

View full text Add to dashboard Cite

Mutually exclusive splicing of exons is a mechanism of functional gene and protein diversification with pivotal roles in organismal development and diseases such as Timothy syndrome, cardiomyopathy and cancer in humans. In order to obtain a first genomewide estimate of the extent and biological role of mutually exclusive splicing in humans, we predicted and subsequently validated mutually exclusive exons (MXEs) using 515 publically available RNA-Seq datasets. Here, we provide evidence for the expression of over 855 MXEs, 42% of which represent novel exons, increasing the annotated human mutually exclusive exome more than fivefold. The data provide strong evidence for the existence of large and multi-cluster MXEs in higher vertebrates and offer new insights into MXE evolution. More than 82% of the MXE clusters are conserved in mammals, and five clusters have homologous clusters in Drosophila. Finally, MXEs are significantly enriched in pathogenic mutations and their spatio-temporal expression might predict human disease pathology.

show abstract

Conservation and regulation of alternative splicing by dynamic inter- and intra-intron base pairings in Lepidoptera 14-3-3z pre-mRNAs

Abstract: (2012) Conservation and regulation of alternative splicing by dynamic inter-and intra-intron base pairings in Lepidoptera 14-3-3z premRNAs, RNA Biology, 9:5, 691-700,

Cited by 10 publications

References 44 publications

The landscape of human mutually exclusive splicing

The landscape of human mutually exclusive splicing

Mutually exclusive alternative splicing of pre‐mRNAs

The landscape of human mutually exclusive splicing

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