2026-06-14T10:37:40Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/54032024-10-31T11:54:37Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605col_20.500.12105_19607
Repisalud
author
Abascal, Federico
author
Ezkurdia, Iakes
author
Rodriguez-Rivas, Juan
author
Manuel Rodriguez, Jose
author
del Pozo, Angela
author
Vazquez, Jesus
author
Valencia, Alfonso
author
Tress, Michael L.
funder
National Institutes of Health (Estados Unidos)
funder
Ministerio de Ciencia e Innovación (España)
funder
Instituto de Salud Carlos III
2017-11-27T13:49:51Z
2017-11-27T13:49:51Z
2015
PLoS Comput Biol. 2015; 11(6):e1004325
10.1371/journal.pcbi.1004325
1553-7358
1553-734X
PLoS Computational Biology
26061177
http://hdl.handle.net/20.500.12105/5403
Alternative splicing of messenger RNA can generate a wide variety of
mature RNA transcripts, and these transcripts may produce protein
isoforms with diverse cellular functions. While there is much supporting
evidence for the expression of alternative transcripts, the same is not
true for the alternatively spliced protein products. Large-scale mass
spectroscopy experiments have identified evidence of alternative
splicing at the protein level, but with conflicting results. Here we
carried out a rigorous analysis of the peptide evidence from eight
large-scale proteomics experiments to assess the scale of alternative
splicing that is detectable by high-resolution mass spectroscopy. We
find fewer splice events than would be expected: we identified peptides
for almost 64\% of human protein coding genes, but detected just 282
splice events. This data suggests that most genes have a single dominant
isoform at the protein level. Many of the alternative isoforms that we
could identify were only subtly different from the main splice isoform.
Very few of the splice events identified at the protein level disrupted
functional domains, in stark contrast to the two thirds of splice events
annotated in the human genome that would lead to the loss or damage of
functional domains. The most striking result was that more than 20\% of
the splice isoforms we identified were generated by substituting one
homologous exon for another. This is significantly more than would be
expected from the frequency of these events in the genome. These
homologous exon substitution events were remarkably conserved-all the
homologous exons we identified evolved over 460 million years ago-and
eight of the fourteen tissue-specific splice isoforms we identified were
generated from homologous exons. The combination of proteomics evidence,
ancient origin and tissue-specific splicing indicates that isoforms
generated from homologous exons may have important cellular roles.
eng
MASS-SPECTROMETRY
DILATED CARDIOMYOPATHY
CODING GENES
PROTEOMICS
ISOFORMS
IDENTIFICATION
VERTEBRATES
ANNOTATION
SEQUENCES
GENOME
Alternatively Spliced Homologous Exons Have Ancient Origins and Are
Highly Expressed at the Protein Level
journal article
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AlternativelySplicedHomologousExons_2015.pdf
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AlternativelySplicedHomologousExons_2015_S1_Fig.pdf
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AlternativelySplicedHomologousExons_2015_S1_Table.pdf
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AlternativelySplicedHomologousExons_2015_S2_Fig.pdf
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AlternativelySplicedHomologousExons_2015_S3_Fig.pdf
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