The spliceosome as a transposon sensor

Dumesic, Phillip A.; Madhani, Hiten

doi:10.4161/rna.26800

Cited by 14 publications

(14 citation statements)

References 86 publications

(106 reference statements)

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“…The presence of suboptimal splice sites in transposons’ transcripts could lead to stalling of the spliceosome, which produces partial or incomplete mRNA precursors and consequent triggering of the siRNA/piRNA response [66]. It can be speculated that similar mechanisms could be involved in the control of Bari3 transposition.…”

Section: Discussionmentioning

confidence: 99%

The Drosophila mojavensis Bari3 transposon: distribution and functional characterization

et al. 2014

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BackgroundBari-like transposons belong to the Tc1-mariner superfamily, and they have been identified in several genomes of the Drosophila genus. This transposon’s family has been used as paradigm to investigate the complex dynamics underlying the persistence and structural evolution of transposable elements (TEs) within a genome. Three structural Bari variants have been identified so far and can be distinguished based on the organization of their terminal inverted repeats. Bari3 is the last discovered member of this family identified in Drosophila mojavensis, a recently emerged species of the Repleta group of the genus Drosophila.ResultsWe studied the insertion pattern of Bari3 in different D. mojavensis populations and found evidence of recent transposition activity. Analysis of the transposase domains unveiled the presence of a functional nuclear localization signal, as well as a functional binding domain. Using luciferase-based assays, we investigated the promoter activity of Bari3 as well as the interaction of its transposase with its left terminus. The results suggest that Bari3 is transposition-competent. Finally we demonstrated transposase transcript processing when the transposase gene is overexpressed in vivo and in vitro.ConclusionsBari3 displays very similar structural and functional features with its close relative, Bari1. Our results strongly suggest that Bari3 is an independent element that has generated genomic diversity in D. mojavensis. It can autonomously transcribe its transposase gene, which in turn can localize in the nucleus and bind the terminal inverted repeats of the transposon. Nevertheless, the identification of an unpredicted spliced form of the Bari3 transposase transcript allows us to hypothesize a control mechanism of its mobility based on mRNA processing. These results will aid the studies on the Bari family of transposons, which is intriguing for its widespread diffusion in Drosophilids coupled with a structural diversity generated during the evolution of Bari-like elements in their host genomes.

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Section: Discussionmentioning

confidence: 99%

The Drosophila mojavensis Bari3 transposon: distribution and functional characterization

et al. 2014

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“…This idea has been inspired by the recent findings of Dumesic and Madhani (Dumesic and Madhani, 2013; Dumesic et al, 2013) that in Cryptococcus yeast, the production of siRNAs is mechanistically linked to mRNA splicing. A connection between siRNA-mediated gene silencing and RNA splicing has been reported also for other organisms, including fission yeast and plants (Bayne et al, 2008; Lee et al, 2013; Tabach et al, 2013; Zhang et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Inspection of the published transposition-competent plant and fungal hAT TEs revealed the presence of ENEs in intronless, but not in intron-containing, transposase genes. We consider the possibility that ENEs compensate for intron loss by TE genes, which occurs evolutionarily because of the coupling of TE silencing to RNA splicing in lower eukaryotes (Dumesic and Madhani, 2013; Dumesic et al, 2013). …”

Section: Introductionmentioning

confidence: 99%

Myriad Triple-Helix-Forming Structures in the Transposable Element RNAs of Plants and Fungi

2016

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SUMMARY The ENE (element for nuclear expression) is a cis-acting RNA structure that protects viral or cellular noncoding (nc)RNAs from nuclear decay through triple-helix formation with the poly(A) tail or 3′-terminal A-rich tract. We expanded the roster of 9 known ENEs by bioinformatic identification of ~200 distinct ENEs that reside in transposable elements (TEs) of numerous non-metazoan and one fish species, and in four Dicistrovirus genomes. Despite variation within the ENE core, none of the predicted triple-helical stacks exceeds five base triples. Increased accumulation of reporter transcripts in human cells demonstrated functionality for representative ENEs. Location close to the poly(A) tail argues that ENEs are active in TE transcripts. Their presence in intronless but not intron-containing hAT transposase genes supports the idea that TEs acquired ENEs to counteract the RNA-destabilizing effects of intron loss, a potential evolutionary consequence of TE horizontal transfer in organisms that couple RNA silencing to splicing deficits.

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“…Increasing evidence has shown that exon‐intron boundary elements in the genomic sequence have played an important role in maintaining an active chromatin conformation in controlling gene expression (43, 47). In our study, we assume that the histone mark of the nucleosome might act to guide DNA methyltransferases resulting in higher methylation levels on the “naked” exons of transgene (cDNA vector), whereas inclusion of noncoding introns shows a potential ability to protect transcripts from silencing (48, 49). This phenomenon might explain why intron‐containing rhodopsin shows reduced methylation and a suppression of repressive histone modifications when associated with the genomic rhodopsin as opposed to the intronless rhodopsin cDNA construct.…”

Section: Discussionmentioning

confidence: 99%

Nanoparticle‐mediated rhodopsin cDNA but not intron‐containing DNA delivery causes transgene silencing in a rhodopsin knockout model

et al. 2015

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Previously, we compared the efficacy of nanoparticle (NP)-mediated intron-containing rhodopsin (sgRho) vs. intronless cDNA in ameliorating retinal disease phenotypes in a rhodopsin knockout (RKO) mouse model of retinitis pigmentosa. We showed that NPmediated sgRho delivery achieved long-term expression and phenotypic improvement in RKO mice, but not NP housing cDNA. However, the protein level of the NPsgRho construct was only 5-10% of wild-type at 8 mo postinjection. To have a better understanding of the reduced levels of long-term expression of the vectors, in the present study, we evaluated the epigenetic changes of subretinal delivering NP-cDNA vs. NP-sgRho in the RKO mouse eyes. Following the administration, DNA methylation and histone status of specific regions (bacteria plasmid backbone, promoter, rhodopsin gene, and scaffold/ matrix attachment region) of the vectors were evaluated at various time points. We documented that epigenetic transgene silencing occurred in vector-mediated gene transfer, which were caused by the plasmid backbone and the cDNA of the transgene, but not the intron-containing transgene. No toxicity or inflammation was found in the treated eyes. Our results suggest that cDNA of the rhodopsin transgene and bacteria backbone interfered with the host defense mechanism of DNA methylation-mediated transgene silencing through heterochromatin-associated modifications.-Zheng, M., Mitra, R. N., Filonov, N. A., Han, Z. Nanoparticle-mediated rhodopsin cDNA but not intron-containing DNA delivery causes transgene silencing in a rhodopsin knockout model. FASEB J. 30, 1076-1086 (2016). www.fasebj.org

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The spliceosome as a transposon sensor

Cited by 14 publications

References 86 publications

The Drosophila mojavensis Bari3 transposon: distribution and functional characterization

The Drosophila mojavensis Bari3 transposon: distribution and functional characterization

Myriad Triple-Helix-Forming Structures in the Transposable Element RNAs of Plants and Fungi

Nanoparticle‐mediated rhodopsin cDNA but not intron‐containing DNA delivery causes transgene silencing in a rhodopsin knockout model

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