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Alternative Splicing Kristin Swihart, BSI Alternative Splicing DNA RNA protein 1 gene 1 protein mRNA A Protein A Initial mRNA B Protein B DNA mRNA mRNA C Protein C Alternative splicing 1 gene several different proteins Alternative Splicing • One gene several different proteins – Average 3.2 transcripts/gene in vertebrates – 59% of vertebrate genes are alternatively spliced • Humans make around 100,000 protein • Sequence shows 20 – 25,000 genes • As molecular knowledge has expanded, we have modified the central dogma. • This is an example of science modifying and refining its theories. Eucaryotic Gene Structure • Eucaryotic genes are composed of interspersed exons and introns – Exons (expressed sequences) – coding black boxes – Introns (interspersed sequences) – removed after transcription blank spaces between the black boxes • In vertebrates, 5% of the gene is exons • Most genes have 8 exons, average length of 145 bp • Introns have an average length of 3365 bp (not junk) Splicing • Introns are removed from the initial transcript • Exons are joined • Mediated by sequences within the intron (GU and AG) • Carried out by a splicesome that is made up of RNAs and proteins. Alternative Splicing • Different exons are included in different transcripts • Many proteins can be made from one gene (changes 1 gene: 1 protein) • Dscam in Drosophila encodes an axon guidance receptor • Gene contains 24 exons • 4 of the exons have different variants • Only one of each exon is included in the final transcript • The gene is able to encode 12 x 48 x 33 x 2 = 38,016 possible proteins. Ways Alternative Splicing is Used • To include only one of several versions of an exon. Only need to code common exons once. • To make 2 completely different proteins by including mutually exclusive exons. Can use the same cellular localization and export signals for both. • The same protein can be targeted to different places in the cell by including different transport signal exons. Only need to encode protein once.
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