RNA Interference
- RNA interference (RNAi) is a form of post-transcriptional modification which occurs in the cytoplasm
- RNAi is sequence-specific silencing of gene expression and therefore can be very precise in silencing certain genes
Small interfering RNA
- In eukaryotes and some prokaryotes, translation of the mRNA produced from target genes can be inhibited by RNA interference (RNAi)
- Small, double-stranded RNA molecules called small interfering RNA (siRNA) bind to mRNA that has been transcribed from target genes (the genes to be ‘silenced’) as their base sequence is complementary
- Each siRNA is attached to a protein complex which is able to breakdown the mRNA that has been transcribed from target genes (the genes to be ‘silenced’)
- Therefore, the mRNA is unable to be translated into proteins
The RNA interference pathway
- Double stranded RNA (dsRNA) is produced by RNA-dependent RNA polymerases (RDRs)
- dsRNA is hydrolysed into smaller fragments, roughly 23 nucleotides long, called small interfering RNAs (siRNAs)
- In the cytoplasm, siRNAs bind to protein complexes which use energy from ATP to separate the two strands of the siRNA
- This exposes the nucleotide bases so they are able to pair with bases from an mRNA molecule
- Once the target mRNA leaves the nucleus and enters the cytoplasm, single-stranded siRNA binds to the target mRNA through complementary base pairing
- The mRNA molecule is cut into fragments by the enzyme/protein complex associated with the siRNA
- Cut mRNA cannot be translated and therefore will not produce proteins
- After the target mRNA has been cut up into fragments, the fragments are broken down into RNA nucleotides by enzymes
The broken-down mRNA fragments can not be translated to produce functional proteins
Therapeutic Application
- siRNAs created against viral genetic material will signal for their degradation and stop the virus from using the host's cellular machinery to replicate itself
- siRNAs can be used in cancer treatment by targeting oncogenes that have been expressed or upregulated
- This reduces the number of proteins produced that can lead to cancer or that maintain cancerous growth
Exam Tip
It is important to state that siRNAs are able to target mRNA through complementary base pairing. The attachment of mRNA to siRNA localises the mRNA to the protein complex which then carries out hydrolysis.
