Introns Early vs' Introns Late

1
Introns Early vs. Introns Late

• Bacterial genomes have no introns
• As organismal complexity increases, so does
  number of introns

2
Introns Early vs. Introns Late

• Were introns lost from bacteria (introns early)
  through evolution?
• Selective advantage
• Loss of introns ? smaller genome ? faster
  replication
• and cell division
• Were introns gained by higher organisms (introns
  late) through evolution?
• Selective advantage
• Alternative splicing ? increased of protein
  isoforms produced
• Exon shuffling ? new genes produced

3
Exons (Frequently) Encode Functional Domains of
Proteins
4
Exon Shuffling

• Recombination events in intron
• Mixing and matching of exons
• New genes
• Transcription and translation of new genes
• New protein with function dependent on combo of
  functional domains

5
Exon Shuffling Gives Rise to New Genes
6
RNA Editing

• Change in the newly transcribed and spliced RNA
  sequence
• Deamination
• Guide-RNA directed uridine insertion or deletion

7
Cytidine Deamination

• Converts a cytosine to uracil
• Catalyzed by cytidine deaminase

8
Cytidine Deamination

• Not a random event specific cytidine residues
  within RNA are targeted

Apolipoprotein B
9
Adenosine Deamination

• Adenosine deamination produces inosine
• Catalyzed by Adenosine Deaminase Acting on RNA
  (ADAR)
• Inosine recognized by translation machinery as a
  guanine

10
Guide RNA-Directed Uridine Insertion or Deletion

• Insertion (or deletion) of Us into RNA sequence
• Us can be contiguous or non-contiguous
• What if the insertion or deletion is not in
  multiples of 3?
• What if the insertion or deletion is in multiples
  of 3?

11
Editing of the coxII Gene
E
N
12
Guide RNAs

• Hybridize to the RNA to be edited, with
  mismatched As looped out from the hybrid

13
mRNA Transport Out of Nucleus

• Translation occurs in the cytoplasm
• mRNAs must be actively transported out of the
  nucleus
• Other RNAs (including excised introns) must
  remain in the nucleus
• Exons are studded with SR proteins
• SR proteins other mRNA-associated proteins
  target mRNA for transport through nuclear pores
  proteins contain nuclear export signals
  recognized by nuclear pore complex