Biochemistry · Molecular Biology (DNA Replication, Repair, Transcription, Translation)

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally. Which mechanism describes how miRNAs most commonly silence target mRNA expression in mammalian cells?

  • A miRNA base-pairs perfectly with target mRNA causing Argonaute 2-mediated cleavage (slicing)
  • B Partial complementarity binding of miRNA in the 3'UTR of target mRNA recruits RISC, causing translational repression and mRNA deadenylation/decay
  • C miRNA binds the 5' cap of target mRNA, preventing ribosome scanning
  • D miRNA is exported from the nucleus to silence homologous genomic sequences by heterochromatin formation
Correct answer: B. Partial complementarity binding of miRNA in the 3'UTR of target mRNA recruits RISC, causing translational repression and mRNA deadenylation/decay

Explanation

In mammals, miRNAs are processed from pri-miRNA (by Drosha/DGCR8 in nucleus) to pre-miRNA to mature miRNA duplex by Dicer in the cytoplasm. The guide strand is loaded into RISC (RNA-induced silencing complex) containing Argonaute proteins. MiRNAs typically bind with imperfect/partial complementarity to the 3'UTR of target mRNAs, recruiting GW182/TNRC6 proteins. This causes: translational repression (reduced ribosome occupancy) and mRNA deadenylation (by CCR4-NOT complex) followed by decapping and 5'→3' exonucleolytic decay. Perfect complementarity (as in plants and siRNA) leads to Argonaute-2 endonuclease (slicer) cleavage. miRNAs do not bind 5' caps or silence genomic DNA directly.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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