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Regulation of constitutive and alternative mRNA splicing across the human transcriptome by PRPF8 is determined by 5′ splice site strength

Overview of attention for article published in Genome Biology (Online Edition), September 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)

Mentioned by

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16 tweeters
facebook
1 Facebook page

Citations

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44 Dimensions

Readers on

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97 Mendeley
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2 CiteULike
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Title
Regulation of constitutive and alternative mRNA splicing across the human transcriptome by PRPF8 is determined by 5′ splice site strength
Published in
Genome Biology (Online Edition), September 2015
DOI 10.1186/s13059-015-0749-3
Pubmed ID
Authors

Vihandha O. Wickramasinghe, Mar Gonzàlez-Porta, David Perera, Arthur R. Bartolozzi, Christopher R. Sibley, Martina Hallegger, Jernej Ule, John C. Marioni, Ashok R. Venkitaraman

Abstract

Sequential assembly of the human spliceosome on RNA transcripts regulates splicing across the human transcriptome. The core spliceosome component PRPF8 is essential for spliceosome assembly through its participation in ribonucleoprotein (RNP) complexes for splice-site recognition, branch-point formation and catalysis. PRPF8 deficiency is linked to human diseases like retinitis pigmentosa or myeloid neoplasia, but its genome-wide effects on constitutive and alternative splicing remain unclear. Here, we show that alterations in RNA splicing patterns across the human transcriptome that occur in conditions of restricted cellular PRPF8 abundance are defined by the altered splicing of introns with weak 5' splice sites. iCLIP of spliceosome components reveals that PRPF8 depletion decreases RNP complex formation at most splice sites in exon-intron junctions throughout the genome. However, impaired splicing affects only a subset of human transcripts, enriched for mitotic cell cycle factors, leading to mitotic arrest. Preferentially retained introns and differentially used exons in the affected genes contain weak 5' splice sites, but are otherwise indistinguishable from adjacent spliced introns. Experimental enhancement of splice-site strength in mini-gene constructs overcomes the effects of PRPF8 depletion on the kinetics and fidelity of splicing during transcription. Competition for PRPF8 availability alters the transcription-coupled splicing of RNAs in which weak 5' splice sites predominate, enabling diversification of human gene expression during biological processes like mitosis. Our 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.

Twitter Demographics

The data shown below were collected from the profiles of 16 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 97 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 2 2%
Sweden 1 1%
South Africa 1 1%
Unknown 93 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 29 30%
Researcher 19 20%
Student > Master 15 15%
Student > Bachelor 7 7%
Professor 4 4%
Other 13 13%
Unknown 10 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 38 39%
Agricultural and Biological Sciences 35 36%
Pharmacology, Toxicology and Pharmaceutical Science 3 3%
Medicine and Dentistry 3 3%
Engineering 2 2%
Other 5 5%
Unknown 11 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 July 2016.
All research outputs
#2,328,019
of 15,383,396 outputs
Outputs from Genome Biology (Online Edition)
#1,798
of 3,319 outputs
Outputs of similar age
#43,421
of 250,073 outputs
Outputs of similar age from Genome Biology (Online Edition)
#1
of 1 outputs
Altmetric has tracked 15,383,396 research outputs across all sources so far. Compared to these this one has done well and is in the 84th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,319 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.1. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 250,073 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them