RNA interference

Meaning: RNAi is post-transcriptional gene silencing. The enzyme Dicer cuts double-stranded RNA into fragments of about 21 to 23 nucleotides, called siRNA. miRNA is similar but comes from hairpin-shaped precursors transcribed from the cell's own genes. One strand is loaded into the RISC complex, which contains the protein Argonaute. This guide strand base-pairs with a complementary mRNA. Near-perfect pairing usually leads to cleavage of the mRNA. Partial pairing, typical of animal miRNAs, mainly blocks translation or promotes mRNA breakdown. Either way, less protein is made.

On the MCAT: A passage adds an siRNA to cultured cells to silence a gene, then asks what happens. Expect to predict that the target mRNA or protein level falls, while the gene's DNA sequence is unchanged and the gene is still transcribed. Other questions ask how a mismatched siRNA would behave (weaker or no silencing), what happens if Dicer is missing (no silencing from double-stranded RNA), or how RNAi can be used to test a gene's function.

Common confusion: RNAi is not a mutation or a gene deletion. The mRNA is made, then destroyed or blocked, so silencing is often partial. That makes it a knockdown, not a knockout. Also keep the enzymes straight: Dicer makes the small RNAs, and RISC uses them to find the target mRNA.