1.3.4

RNA Processing in Eukaryotes

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RNA Processing in Eukaryotes

Before the information in eukaryotic mRNA is translated into protein, it is modified or edited in several ways

mRNA processing

mRNA processing

  • The initial mRNA molecule produced in eukaryotic transcription is known as "pre-mRNA".
  • The eukaryotic pre-mRNA undergoes extensive processing before it is ready to be translated.
  • The additional steps involved in eukaryotic mRNA maturation create a molecule with a much longer half-life than a prokaryotic mRNA.
    • Eukaryotic mRNAs last for several hours, whereas the typical E. coli mRNA lasts no more than five seconds.
5' capping

5' capping

  • While the pre-mRNA is still being synthesized, a 7-methylguanosine cap is added to the 5' end of the growing transcript by a phosphate linkage.
    • This is sometimes more simply called a "GTP cap".
  • This moiety (functional group) protects the nascent mRNA from degradation.
    • In addition, factors involved in protein synthesis recognize the cap to help initiate translation by ribosomes.
3' poly-A tail

3' poly-A tail

  • Once elongation is complete, the pre-mRNA is cleaved by an endonuclease between an AAUAAA consensus sequence and a GU-rich sequence.
    • This leaves the AAUAAA sequence on the pre-mRNA.
  • An enzyme called poly-A polymerase then adds a string of approximately 200 A residues, called the poly-A tail.
  • This modification further protects the pre-mRNA from degradation.
  • The poly-A tail also signals the export of the cellular factors that the transcript needs to the cytoplasm.
Pre-mRNA splicing

Pre-mRNA splicing

  • Eukaryotic genes are composed of exons and introns.
    • Exons correspond to protein-coding sequences.
    • Introns do not encode functional proteins. They may be involved in gene regulation but are removed from the pre-mRNA during processing.
  • The process of removing introns and reconnecting exons is called splicing.
Pre-mRNA splicing - 2

Pre-mRNA splicing - 2

  • Splicing removes and degraded introns while the pre-mRNA is still in the nucleus.
  • Splicing occurs by a sequence-specific mechanism that ensures introns will be removed and exons rejoined.
    • The splicing of pre-mRNAs is conducted by complexes of proteins and RNA molecules called spliceosomes.
  • Spliceosomes are composed of proteins and RNA molecules called snRNAs.
  • Spliceosomes recognize sequences at the 5' and 3' end of the intron.
Alternative splicing

Alternative splicing

  • Splicing can produce many different mRNA molecules from a single pre-mRNA molecule.
  • This is because the pattern of exons and introns can be reordered during splicing.
    • This is known as alternative splicing.
  • Alternative splicing plays a role in gene regulation and increases the diversity of proteins that can be produced from a single gene.
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