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Biochemistry · Molecular biology: RNA interference
Sample itemPatisiran, a double-stranded small interfering RNA given intravenously for hereditary transthyretin amyloidosis, lowers circulating transthyretin. Which mechanism applies?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
A. The guide strand loads into RISC and pairs with transthyretin mRNA, which Argonaute cleaves
Small interfering RNAs are loaded into the RNA-induced silencing complex. The guide strand pairs with near-perfect complementarity to its target mRNA and Argonaute cleaves the transcript, lowering protein synthesis. MicroRNAs use the same complex but pair imperfectly, causing translational repression and mRNA decay.
Option by option
A. The guide strand loads into RISC and pairs with transthyretin mRNA, which Argonaute cleaves (correct)
Correct. RISC-guided cleavage of the target mRNA is the mechanism of an siRNA.
B. The drug binds the promoter of the transthyretin gene and blocks RNA polymerase II
RNA interference acts after transcription on mRNA and does not block the promoter.
C. The drug is reverse transcribed into DNA that silences the gene
siRNA is not reverse transcribed, and human cells do not integrate it into DNA.
D. The drug blocks ribosome binding by attaching to the 5' cap of mRNA
The siRNA does not target the 5' cap, and it works by complementary pairing with mRNA.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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