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Splice-site pairing is an intrinsically high fidelity process.

ABSTRACT: The extensive alternative splicing in higher eukaryotes has initiated a debate whether alternative mRNA isoforms are generated by an inaccurate spliceosome or are the consequence of highly degenerate splice sites within the human genome. Here, we established a quantitative assay to evaluate the accuracy of splice-site pairing by determining the number of incorrect exon-skipping events made from constitutively spliced pre-mRNA transcripts. We demonstrate that the spliceosome pairs exons with an astonishingly high degree of accuracy that may be limited by the quality of pre-mRNAs generated by RNA pol II. The error rate of exon pairing is increased by the effects of the neurodegenerative disorder spinal muscular atrophy because of reduced levels of Survival of Motor Neuron, a master assembler of spliceosomal components. We conclude that all multi-intron-containing genes are alternatively spliced and that the reduction of SMN results in a general splicing defect that is mediated through alterations in the fidelity of splice-site pairing.

SUBMITTER: Fox-Walsh KL

PROVIDER: S-EPMC2644112 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Splice-site pairing is an intrinsically high fidelity process.

Fox-Walsh Kristi L KL Hertel Klemens J KJ

Proceedings of the National Academy of Sciences of the United States of America 20090129 6

The extensive alternative splicing in higher eukaryotes has initiated a debate whether alternative mRNA isoforms are generated by an inaccurate spliceosome or are the consequence of highly degenerate splice sites within the human genome. Here, we established a quantitative assay to evaluate the accuracy of splice-site pairing by determining the number of incorrect exon-skipping events made from constitutively spliced pre-mRNA transcripts. We demonstrate that the spliceosome pairs exons with an a ...[more]

PMID: 19179398

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Project description:Information on site fidelity and ranging patterns of wild animals is critical to understand how they use their environment and guide conservation and management strategies. Delphinids show a wide variety of site fidelity and ranging patterns. Between September 2013 and October 2015, we used boat-based surveys, photographic identification, biopsy sampling, clustering analysis, and geographic information systems to determine the site-fidelity patterns and representative ranges of southern Australian bottlenose dolphins (Tursiops cf. australis) inhabiting the inner area of Coffin Bay, a highly productive inverse estuary located within Thorny Passage Marine Park, South Australia. Agglomerative hierarchical clustering (AHC) of individuals' site-fidelity index and sighting rates indicated that the majority of dolphins within the inner area of Coffin Bay are "regular residents" (n = 125), followed by "occasional residents" (n = 28), and "occasional visitors" (n = 26). The low standard distance deviation indicated that resident dolphins remained close to their main center of use (range = 0.7-4.7 km, X ± SD = 2.3 ± 0.9 km). Representative ranges of resident dolphins were small (range = 3.9-33.5 km2, X ± SD = 15.2 ± 6.8 km2), with no significant differences between males and females (Kruskal-Wallis, ?2 = 0.426, p = .808). The representative range of 56% of the resident dolphins was restricted to a particular bay within the study area. The strong site fidelity and restricted ranging patterns among individuals could be linked to the high population density of this species in the inner area of Coffin Bay, coupled with differences in social structure and feeding habits. Our results emphasize the importance of productive habitats as a major factor driving site fidelity and restricted movement patterns in highly mobile marine mammals and the high conservation value of the inner area of Coffin Bay for southern Australian bottlenose dolphins.

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Splice-site pairing is an intrinsically high fidelity process.

Publications

Splice-site pairing is an intrinsically high fidelity process.

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