Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery.

@article{Papasaikas2015FunctionalSN,
  title={Functional splicing network reveals extensive regulatory potential of the core spliceosomal machinery.},
  author={Panagiotis K. Papasaikas and Juan Ram{\'o}n Tejedor and Luisa Vigevani and Juan Valc{\'a}rcel},
  journal={Molecular cell},
  year={2015},
  volume={57 1},
  pages={
          7-22
        }
}
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130 Citations
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130 Citations

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This study investigates the protein connectivity of SR and hnRNP proteins to the core spliceosome using probabilistic network reconstruction based on the integration of interactome and gene expression data and suggests that activators promote the formation of PPIs between splicesomal sub-complexes, whereas repressors mostly operate through protein-RNA interactions.
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It is argued for the existence of a compensatory mechanism enabling cells to cope with drastic perturbations in core splicing components and maintain the correct balance of spliceosomal snRNPs through differential expression of variant (v)U-snRNPs.
Blocking late stages of splicing quickly limits pre-spliceosome assembly in vivo
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The results show that knocking down a splicing factor can quickly lead to a recycling defect with splicing factors sequestered in stalled complexes, thereby limiting new rounds of splicing, and demonstrate that this ‘feed-back’ effect can be minimized by depleting the target protein more gradually or only partially, allowing a better separation between primary and secondary effects.
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Small molecule inhibitors that target components of the spliceosome have great potential as tools to probe splicing mechanism and dissect splicing regulatory networks in cells. These compounds also…
Network theory reveals principles of spliceosome structure and dynamics.
Regulation of constitutive and alternative mRNA splicing across the human transcriptome by PRPF8 is determined by 5′ splice site strength
TLDR
These findings exemplify the regulatory potential of changes in the core spliceosome machinery, which may be relevant to slow-onset human genetic diseases linked to PRPF8 deficiency, and alter the transcription-coupled splicing of RNAs in which weak 5′ splice sites predominate.
RBM17 Interacts with U2SURP and CHERP to Regulate Expression and Splicing of RNA-Processing Proteins
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References

SHOWING 1-10 OF 66 REFERENCES
Regulation of alternative splicing by the core spliceosomal machinery.
TLDR
A role for the core spliceosomal machinery in controlling an exon network that appears to modulate the levels of many RNA processing factors is demonstrated.
Manipulation of Alternative Splicing by a Newly Developed Inhibitor of Clks*
TLDR
TG003, a novel inhibitor of Clk family will be a valuable tool to dissect the regulatory mechanisms involving serine/arginine-rich protein phosphorylation signaling pathways in vivo, and may be applicable for the therapeutic manipulation of abnormal splicing.
Deciphering the splicing code
TLDR
The assembly of a ‘splicing code’ is described, which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons and facilitates the discovery and detailed characterization of regulatedAlternative splicing events on a genome-wide scale.
Alternative spliceosome assembly pathways revealed by single-molecule fluorescence microscopy.
Comprehensive proteomic analysis of the human spliceosome
TLDR
The spliceosome is identified as the most complex cellular machine so far characterized, containing at least 30 proteins with known or putative roles in gene expression steps other than splicing, and its components comprise all previously known splicing factors and 58 newly identified components.
Genome-wide identification of Fas/CD95 alternative splicing regulators reveals links with iron homeostasis.
Transcript Specificity in Yeast Pre-mRNA Splicing Revealed by Mutations in Core Spliceosomal Components
TLDR
A microarray-based approach to examine the effects of mutations in 18 highly conserved core components of the spliceosomal machinery reveals clear differences in the splicing defects of particular pre-mRNA substrates, which may offer an important opportunity for yeast to regulate gene expression in a transcript-dependent fashion.
Isolation of an active step I spliceosome and composition of its RNP core
TLDR
Insight is provided into the spliceosome’s catalytic RNP domain and a central role for the aforementioned proteins in sustaining its catalytically active structure is indicated.
The Spliceosome: Design Principles of a Dynamic RNP Machine
Spliceostatin A targets SF3b and inhibits both splicing and nuclear retention of pre-mRNA
TLDR
The natural product FR901464 and its methylated derivative, spliceostatin A are shown to inhibit in vitro splicing and promote pre-mRNA accumulation by binding to SF3b, a subcomplex of the U2 small nuclear ribonucleoprotein in the spliceosome.
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