A 5′ Splice Site Enhances the Recruitment of Basal Transcription Initiation Factors In Vivo

Damgaard, Christian Kroun; Kahns, Søren; Lykke‐Andersen, Søren; Nielsen, Anders Lade; Jensen, Torben Heick; Kjems, Jørgen

doi:10.1016/j.molcel.2007.11.035

Cited by 151 publications

(163 citation statements)

References 24 publications

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“…The interaction between the transcriptional and splicing machinery may be functionally relevant because different promoters can yield transcripts that are subject to differential alternative splicing (69,70). Although many studies have focused on the effect of transcription factors in splicing, there is also increasing evidence that promoter-proximal splicing elements can influence transcription (26,28,71).…”

Section: Gro Interactors Include Chromatin Remodelers Protein Kinasementioning

confidence: 99%

The Central Region of the Drosophila Co-repressor Groucho as a Regulatory Hub

Kwong

Chambers

Vashisht

et al. 2015

Journal of Biological Chemistry

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Background:The co-repressor Groucho has an essential, but disordered, central region. Results: We identified over 160 central region-binding proteins, many of which, including components of the spliceosome, modulate Groucho-mediated repression. Conclusion: Groucho regulates transcription by multiple mechanisms and may link the transcriptional and splicing machineries. Significance: Its central region may serve as the hub of a regulatory network.

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Section: Gro Interactors Include Chromatin Remodelers Protein Kinasementioning

confidence: 99%

The Central Region of the Drosophila Co-repressor Groucho as a Regulatory Hub

Kwong

Chambers

Vashisht

et al. 2015

Journal of Biological Chemistry

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“…Its human homolog, CAPER, has been proposed to couple transcription with splicing, influencing alternative splicing of the steroid hormone receptor (9,13). Because both the presence of a 5=SS and the binding of snRNPs have been shown to enhance transcription (8), the mechanism by which CAPER can stimulate transcription may be related to its role in U1 binding.…”

Section: Discussionmentioning

confidence: 99%

A U1-U2 snRNP Interaction Network during Intron Definition

Shao

Kim

Cao

et al. 2012

Molecular and Cellular Biology

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The assembly of prespliceosomes is responsible for selection of intron sites for splicing. U1 and U2 snRNPs recognize 5= splice sites and branch sites, respectively; although there is information regarding the composition of these complexes, little is known about interaction among the components or between the two snRNPs. Here we describe the protein network of interactions linking U1 and U2 snRNPs with the ATPase Prp5, important for branch site recognition and fidelity during the first steps of the reaction, using fission yeast Schizosaccharomyces pombe. The U1 snRNP core protein U1A binds to a novel SR-like protein, Rsd1, which has homologs implicated in transcription. Rsd1 also contacts S. pombe Prp5 (SpPrp5), mediated by SR-like domains in both proteins. SpPrp5 then contacts U2 snRNP through SF3b, mediated by a conserved DPLD motif in Prp5. We show that mutations in this motif have consequences not only in vitro (defects in prespliceosome formation) but also in vivo, yielding intron retention and exon skipping defects in fission yeast and altered intron recognition in budding yeast Saccharomyces cerevisiae, indicating that the U1-U2 network provides critical, evolutionarily conserved contacts during intron definition. Intron removal from new transcripts by pre-mRNA splicing is a fundamental feature of all eukaryotes. Such splicing is catalyzed by the spliceosome, a dynamic RNA-protein complex containing Ͼ150 proteins and five snRNAs. The assembly of the spliceosome is considered to be a dynamic process with a large number of RNA-RNA and RNA-protein rearrangements (31, 35). In the canonical pathway, U1 snRNP recognizes the pre-mRNA at the 5= splice site (5=SS); then, U2 snRNP stably binds the branch site (BS) region to form a prespliceosome. U4/5/6 tri-snRNP then joins, after rearrangements, U1 and U4 snRNPs are released, and the remaining U2/5/6 core forms the catalytic spliceosome. Both the early recognition of pre-mRNA and the rearrangements of snRNP structures to form an active conformation are facilitated by DExD/H ATPases, which couple ATP binding/hydrolysis with structural alterations (33,35).Two modes for early exon and intron specification have been described: exon definition for short exons flanked by long introns, which mostly appear in vertebrates, and intron definition for short introns, which are often present in lower eukaryotes (5). Interactions between U1 and U2 snRNPs are critical to both exonand intron-defined phases of spliceosome assembly. In the formation of commitment complexes in budding yeast Saccharomyces cerevisiae, or E complexes in mammals, cross-intron bridging interactions are proposed to connect from Prp40 in U1 snRNP at the 5=SS to SF1/BBP at the branch site or to U2AF at the polypyrimidine tract (PPT), respectively (1, 24). However, in prespliceosome formation, the first ATP-dependent transition, the BS-SF1/BBP interaction (or the PPT-U2AF interaction) is disrupted and replaced by BS-U2 snRNP interactions (28,33). This exchange of interactions is facilitated by the ATPase Prp...

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“…Nevertheless, increasing evidence has established that a reciprocal and mutually beneficial coupling exists between transcription and RNA processing. Promoter strength may influence alternative splicing ("forward coupling") and splicing can stimulate transcription ("reverse coupling") (Damgaard et al, 2008;Pandit et al, 2008). The influence that the splicing process exerts on transcription seems not to be restricted only to transcription initiation, but also involves the elongation phase (Pandit et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

“…The influence that the splicing process exerts on transcription seems not to be restricted only to transcription initiation, but also involves the elongation phase (Pandit et al, 2008). This observation implies that, besides mutations involving promoter proximal splice sites, known to influence transcription (Damgaard et al, 2008), also splicing mutations involving distal splice sites could theoretically affect transcriptional efficiency. This mechanism might represent a relevant modifier of pathogenic consequences of regulatory splicing mutations.…”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of novel collagen VI non-canonical splicing mutations causing ullrich congenital muscular dystrophy

Martoni

Urciuolo

Sabatelli³

et al. 2009

Hum. Mutat.

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Splicing mutations occurring outside the invariant GT and AG dinucleotides are frequent in disease genes and the definition of their pathogenic potential is often challenging. We have identified four patients affected by Ullrich congenital muscular dystrophy and carrying unusual mutations of COL6 genes affecting RNA splicing. In three cases the mutations occurred in the COL6A2 gene and consisted of nucleotide substitutions within the degenerated sequences flanking the canonical dinucleotides. In the fourth case, a genomic deletion occurred which removed the exon8-intron8 junction of the COL6A1 gene. These mutations induced variable splicing phenotypes, consisting of exon skipping, intron retention and cryptic splice site activation/usage. A quantitative RNA assay revealed a reduced level of transcription of the mutated in-frame mRNA originating from a COL6A2 point mutation at intronic position +3. At variance, the transcription level of the mutated in-frame mRNA originating from a genomic deletion which removed the splicing sequences of COL6A1 exon 8 was normal. These findings suggest a different transcriptional efficiency of a regulatory splicing mutation compared to a genomic deletion causing a splicing defect.

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A 5′ Splice Site Enhances the Recruitment of Basal Transcription Initiation Factors In Vivo

Cited by 151 publications

References 24 publications

The Central Region of the Drosophila Co-repressor Groucho as a Regulatory Hub

The Central Region of the Drosophila Co-repressor Groucho as a Regulatory Hub

A U1-U2 snRNP Interaction Network during Intron Definition

Identification and characterization of novel collagen VI non-canonical splicing mutations causing ullrich congenital muscular dystrophy

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