Splicing, RNA Export, and the Genetic Code

Splicing & Exporting RNA & Reading the Genetic Code

Splicing Reactions & snRNA

  • Splicing is a process that removes introns from pre-mRNA to produce mature mRNA containing only exons (expressed sequences).
  • This process is carried out by a complex called the spliceosome, which consists of five small nuclear RNAs (snRNAs) and hundreds of proteins.
  • The snRNAs involved are U1, U2, U4, U5, and U6. They complex with proteins to form snRNPs (small nuclear ribonucleoproteins), also known as "snurps".
  • snRNAs form the catalytic site of the spliceosome, which is assembled de novo on each mRNA molecule.
  • Three key splicing sequences in the pre-mRNA base-pair with snRNA: the 5’ splice site, the 3’ splice site, and the branch point. The consensus sequences include R (A or G/purine) and Y (C or U/pyrimidine).

Steps in Splicing

The spliceosome carries out ATP-driven events to recognize, position, and cleave splice sites:

  1. U1 snRNP Binding: U1 snRNP binds to the 5' splice site, and proteins bind to other sites.
  2. U2 snRNP Binding: U2 snRNP binds to the branch point site, causing an adenosine to bulge out.
  3. snRNP Complex Entry: A U4/6 pair and U5 snRNPs enter, and U6 replaces U1 at the 5' splice site. U4 and U1 are released.
  4. Lariat Formation: The branch point adenosine attacks the 5' splice site, forming a new covalent bond and a loop (lariat).
  5. Exon Joining: The newly created 3'OH from the 5' splice site reacts with the 3' splice site to join the exon sequences and release the lariat.
  6. Exon Junction Complex (EJC): The EJC marks the newly completed splicing event.

Splicing Mutations

  • Splicing errors can occur, such as exon skipping or selecting a