Alternative Splicing

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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)
       • Introns are removed
         from the initial
       • 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

                  • 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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