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SUMMARY:Splicing in Drosophila
DTSTART:20200312T120000
DTEND:20200312T130000
DTSTAMP:20260406T224600Z
UID:233668e0dac12fe1c2d86f53112927a468b5de8667b3c6895aa79b1c
CATEGORIES:Conferences - Seminars
DESCRIPTION:Pablo Baeza Centurion\nAlternative pre-mRNA splicing is a regu
 lated step in eukaryotic gene expression in which introns are removed from
  the transcript and exons are joined together to form a mature mRNA. To st
 udy the effects of mutations on alternative splicing\, we built a mutant l
 ibrary containing all combinations of 12 mutations that accumulated during
  the emergence of an alternatively-spliced human exon: FAS exon 6. This al
 lowed us to study the effects of individual nucleotide substitutions in th
 ousands of different closely-related genetic contexts. We show that the ef
 fect of the same mutation on exon inclusion depends non-monotonically on t
 he inclusion levels of the exon before the mutation is made\, with mutatio
 ns having their strongest splice-altering effects in exons with intermedia
 te levels of inclusion\, and their smallest effects in exons that are alwa
 ys skipped or always included. After performing deep mutagenesis in two hi
 ghly included (constitutive) exons\, we find that\, in agreement with our 
 previous results\, mutations have a very small effect on the inclusion of 
 constitutive exons with the exception of mutations in exon-intron boundari
 es (splice sites). Since alternative splicing is frequently perturbed in h
 uman genetic diseases\, we then put these results in a more practical cont
 ext to address the question of the extent to which random mutations in the
  human genome are likely to have splice-altering effects. Since most human
  exons are highly included\, we conclude that a random mutation is unlikel
 y to have a splice altering effect\, and that altered splicing should only
  be considered a likely proximal disease mechanism for mutations that affe
 ct alternatively spliced exons (included at intermediate levels) or disrup
 t splice sites.\n 
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153
STATUS:CONFIRMED
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