Brahma regulates a specific trans-splicing event at the<i>mod(mdg4)</i>locus of<i>Drosophila melanogaster</i>

Yu, Simei; Waldholm, Johan; Böhm, Stefanie; Visa, Neus

doi:10.4161/rna.27866

Cited by 17 publications

(22 citation statements)

References 38 publications

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“…TSB association with chromatin proteins implies that TSB-specific enhancement of transsplicing could be regulated by transcription and could explain the observed regulation of trans-spliced mod(mdg4) isoform abundance by Brahma, the ATPase subunit of the SWI/SNF chromatin remodeling complex, and the local density of RNA polymerase II (Yu et al 2014).…”

Section: Discussionmentioning

confidence: 99%

“…The mod(mdg4) gene has at least 31 identified 3 ′ exons, which are located in several regions transcribed from both DNA strands (Yu et al 2014). Using the splice sitefinding software Human Splicing Finder (HSF) (Desmet et al 2009), we found no strong 5 ′ SS sequences in introns between the alternatively trans-spliced exons except the identified internal cis-spliced introns (Supplemental Fig.…”

Section: Lack Of Amentioning

confidence: 97%

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A conserved intronic U1 snRNP-binding sequence promotestrans-splicing inDrosophila

et al. 2015

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Unlike typical cis-splicing, trans-splicing joins exons from two separate transcripts to produce chimeric mRNA and has been detected in most eukaryotes. Trans-splicing in trypanosomes and nematodes has been characterized as a spliced leader RNA-facilitated reaction; in contrast, its mechanism in higher eukaryotes remains unclear. Here we investigate mod(mdg4), a classic trans-spliced gene in Drosophila, and report that two critical RNA sequences in the middle of the last 5 ′ intron, TSA and TSB, promote trans-splicing of mod(mdg4). In TSA, a 13-nucleotide (nt) core motif is conserved across Drosophila species and is essential and sufficient for trans-splicing, which binds U1 small nuclear RNP (snRNP) through strong base-pairing with U1 snRNA. In TSB, a conserved secondary structure acts as an enhancer. Deletions of TSA and TSB using the CRISPR/Cas9 system result in developmental defects in flies. Although it is not clear how the 5 ′ intron finds the 3 ′ introns, compensatory changes in U1 snRNA rescue trans-splicing of TSA mutants, demonstrating that U1 recruitment is critical to promote trans-splicing in vivo. Furthermore, TSA core-like motifs are found in many other trans-spliced Drosophila genes, including lola. These findings represent a novel mechanism of trans-splicing, in which RNA motifs in the 5 ′ intron are sufficient to bring separate transcripts into close proximity to promote trans-splicing.

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Section: Discussionmentioning

confidence: 99%

Section: Lack Of Amentioning

confidence: 97%

A conserved intronic U1 snRNP-binding sequence promotestrans-splicing inDrosophila

et al. 2015

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“…The SWI/SNF remodeler modulates transcription of many genes by altering nucleosome organization at promoter regions (133,134) and in gene bodies (135). SWI/SNF also regulates both splicing and the RNAPII elongation rate by interacting with either spliceosome components or the RNAPIIphosphorylated CTD domain (136)(137)(138)(139)(140). The SWI/SNF ATPase catalytic subunit Brahma (Brm) can interact with U5 snRNP or with Sam68, an hnRNP-like protein that influences exon recognition (136).…”

Section: Chromatin Density and Nucleosome Occupancymentioning

confidence: 99%

“…This interaction facilitates the recruitment of the splicing machinery to variant exons in the CD44 gene with weak splice sites (136). Interestingly, the regulation of gene splicing by Brm is independent of its ATPase activity (140). SAP155, a U2 snRNP component, interacts with WSTF, an ISWI-type chromatin remodeler (139).…”

Section: Chromatin Density and Nucleosome Occupancymentioning

confidence: 99%

Regulation of Alternative Splicing Through Coupling with Transcription and Chromatin Structure

Naftelberg

Schor²,

Ast³

et al. 2015

Annu. Rev. Biochem.

394

354

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Alternative precursor messenger RNA (pre-mRNA) splicing plays a pivotal role in the flow of genetic information from DNA to proteins by expanding the coding capacity of genomes. Regulation of alternative splicing is as important as regulation of transcription to determine cell- and tissue-specific features, normal cell functioning, and responses of eukaryotic cells to external cues. Its importance is confirmed by the evolutionary conservation and diversification of alternative splicing and the fact that its deregulation causes hereditary disease and cancer. This review discusses the multiple layers of cotranscriptional regulation of alternative splicing in which chromatin structure, DNA methylation, histone marks, and nucleosome positioning play a fundamental role in providing a dynamic scaffold for interactions between the splicing and transcription machineries. We focus on evidence for how the kinetics of RNA polymerase II (RNAPII) elongation and the recruitment of splicing factors and adaptor proteins to chromatin components act in coordination to regulate alternative splicing.

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“…They also co-immunoprecipitate with splicing factors and their depletion changes alternative splicing patterns 105; 107; 108; 109; 110 . The effects of the Brm SWI/SNF subunit on splicing correlate with altered pol II pausing, but unexpectedly they are independent of its ATPase activity 105; 108 . It is therefore possible that Brm affects splicing in a chromatin-independent way through its incorporation into hnRNP particles on nascent transcripts 111 .…”

Section: Chromatin Remodelers and Co-transcriptional Splicingmentioning

confidence: 99%

Coupling of RNA Polymerase II Transcription Elongation with Pre-mRNA Splicing

Saldi

Cortázar

Sheridan

et al. 2016

Journal of Molecular Biology

242

226

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Pre-mRNA maturation frequently occurs at the same time and place as transcription by RNA polymerase II (pol II). The co-transcriptionality of mRNA processing has permitted the evolution of mechanisms that functionally couple transcription elongation with diverse events that occur on the nascent RNA. This review summarizes current understanding of the relationship between transcriptional elongation through a chromatin template and co-transcriptional splicing including alternative splicing decisions that affect the expression of most human genes.

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Brahma regulates a specific trans-splicing event at themod(mdg4)locus ofDrosophila melanogaster

Cited by 17 publications

References 38 publications

A conserved intronic U1 snRNP-binding sequence promotestrans-splicing inDrosophila

A conserved intronic U1 snRNP-binding sequence promotestrans-splicing inDrosophila

Regulation of Alternative Splicing Through Coupling with Transcription and Chromatin Structure

Coupling of RNA Polymerase II Transcription Elongation with Pre-mRNA Splicing

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