MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. The mature miRNA strand is incorporated into the RISC complex. What is the MECHANISM of miRNA-mediated gene silencing when the miRNA has partial complementarity to the target mRNA?
- A AGO2 (Argonaute-2) cleaves the mRNA directly (slicing)
- B RISC binds the 3'UTR of target mRNA; translational repression and mRNA deadenylation/decapping leads to mRNA degradation in P-bodies ✓
- C The miRNA directly binds the promoter of the target gene, blocking transcription
- D The miRNA sequesters Dicer in the nucleus, preventing new miRNA processing
Explanation
When miRNA has near-perfect complementarity, AGO2 slices the target mRNA (siRNA-like mechanism). However, animal miRNAs typically have partial complementarity (seed sequence match at positions 2-7 from 5' end of miRNA is critical), binding primarily to 3'UTR of mRNAs. With imperfect pairing, RISC recruits GW182 proteins that recruit deadenylase complexes (CCR4-NOT), removing the poly-A tail, followed by decapping by DCP2, and exonucleolytic degradation from 5'→3'. Repressed mRNAs may also accumulate in cytoplasmic processing bodies (P-bodies). Translational repression at initiation (cap-40S ribosome interaction blocked) also contributes.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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