Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/5403
Título
Alternatively Spliced Homologous Exons Have Ancient Origins and Are
Highly Expressed at the Protein Level
Autor(es)
Abascal, Federico | Ezkurdia, Iakes CNIC | Rodriguez-Rivas, Juan | Manuel Rodriguez, Jose | del Pozo, Angela | Vazquez, Jesus CNIC | Valencia, Alfonso CNIO | Tress, Michael L.
Fecha de publicación
2015
Cita
PLoS Comput Biol. 2015; 11(6):e1004325
Idioma
Inglés
Tipo de documento
journal article
Resumen
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.
Palabras clave
MASS-SPECTROMETRY | DILATED CARDIOMYOPATHY | CODING GENES | PROTEOMICS | ISOFORMS | IDENTIFICATION | VERTEBRATES | ANNOTATION | SEQUENCES | GENOME
Versión en línea
DOI
Aparece en las colecciones
Ficheros en el ítem
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 3.135Mb
- Formato:
- Descripción:
- Artículo
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 651.8Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 75.58Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 62.32Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 32.33Kb
- Formato:
- Microsoft Excel 2007
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 406.3Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 61.23Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 74.73Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 81.44Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 521.3Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 80.81Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 169.7Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 280.4Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 146.5Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 322.6Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 488.4Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 360.9Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 489.6Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 142.0Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 129.2Kb
- Formato:
- Descripción:
- Supl. inf.
- Nombre:
- AlternativelySplicedHomologous ...
- Tamaño:
- 149.2Kb
- Formato:
- Descripción:
- Supl. inf.