What is RNA interference (RNAi) and how do siRNA and miRNA lead to gene silencing?

• A. They are enzymes that cleave DNA directly.
• B. They guide RISC to complementary mRNA to cause degradation or translational repression.
• C. They bind ribosomes to enhance translation.
• D. They modify chromatin to suppress transcription.

Answer: (B)

RNA interference works by using small RNA molecules as guides to recognize specific mRNA and shut down its expression. The small interfering RNA (siRNA) and microRNA (miRNA) are loaded into the RNA-induced silencing complex (RISC). The guide strand within RISC pairs with a complementary sequence on a target mRNA. When the match is nearly perfect, the Argonaute protein in RISC cleaves the mRNA, causing its rapid decay. When the pairing is imperfect, which is common for miRNAs, binding typically blocks translation and promotes mRNA destabilization, leading to lower protein production. This post-transcriptional silencing is the hallmark of RNAi.

The other descriptions don’t fit this mechanism: RNAi does not cleave DNA directly or enhance translation by binding ribosomes, and while chromatin modifications can silence transcription through other pathways, the classic RNAi effect is directed at mRNA in the cytoplasm to reduce or prevent protein synthesis.