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U2AF1 mutations alter sequence specificity of pre-mRNA binding and splicing

Overview of attention for article published in Leukemia (08876924), October 2014
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (51st percentile)

Mentioned by

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1 news outlet
twitter
1 tweeter

Readers on

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38 Mendeley
Title
U2AF1 mutations alter sequence specificity of pre-mRNA binding and splicing
Published in
Leukemia (08876924), October 2014
DOI 10.1038/leu.2014.303
Pubmed ID
Authors

T Okeyo-Owuor, B S White, R Chatrikhi, D R Mohan, S Kim, M Griffith, L Ding, S Ketkar-Kulkarni, J Hundal, K M Laird, C L Kielkopf, T J Ley, M J Walter, T A Graubert, Okeyo-Owuor T, White BS, Chatrikhi R, Mohan DR, Kim S, Griffith M, Ding L, Ketkar-Kulkarni S, Hundal J, Laird KM, Kielkopf CL, Ley TJ, Walter MJ, Graubert TA

Abstract

We previously identified missense mutations in the U2AF1 splicing factor affecting codons S34 (S34F and S34Y) or Q157 (Q157R and Q157P) in 11% of patients with de novo myelodysplastic syndromes (MDS). Although the role of U2AF1 as an accessory factor in the U2 snRNP is well established, it is not yet clear how mutations affect splicing or contribute to MDS pathophysiology. We analyzed splice junctions in RNA-seq data generated from transfected CD34+ hematopoietic cells and found significant differences in the abundance of known and novel junctions in samples expressing mutant U2AF1 (S34F). For selected transcripts, splicing alterations detected by RNA-seq were confirmed by analysis of primary de novo MDS patient samples. These effects were not due to impaired U2AF1 (S34F) localization as it co-localized normally with U2AF2 within nuclear speckles. We further found evidence in the RNA-seq data for decreased affinity of U2AF1 (S34F) for uridine (relative to cytidine) at the e-3 position immediately upstream of the splice acceptor site and corroborated this finding using affinity binding assays. These data suggest that the S34F mutation alters U2AF1 function in the context of specific RNA sequences, leading to aberrant alternative splicing of target genes, some of which may be relevant for MDS pathogenesis.Leukemia accepted article preview online, 14 October 2014. doi:10.1038/leu.2014.303.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter 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 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
Unknown 37 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 13 34%
Researcher 12 32%
Student > Master 5 13%
Professor 2 5%
Student > Postgraduate 2 5%
Other 4 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 23 61%
Biochemistry, Genetics and Molecular Biology 7 18%
Medicine and Dentistry 6 16%
Unspecified 1 3%
Nursing and Health Professions 1 3%
Other 0 0%

Attention Score in Context

This research output has an Altmetric Attention Score of 10. 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 08 November 2014.
All research outputs
#394,729
of 4,480,293 outputs
Outputs from Leukemia (08876924)
#72
of 1,173 outputs
Outputs of similar age
#15,754
of 120,540 outputs
Outputs of similar age from Leukemia (08876924)
#26
of 68 outputs
Altmetric has tracked 4,480,293 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,173 research outputs from this source. They receive a mean Attention Score of 3.2. This one has done particularly well, scoring higher than 92% of its peers.
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 120,540 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 86% of its contemporaries.
We're also able to compare this research output to 68 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.