41. RNA interference is mediated by both siRNA and miRNA. Which one of the following statement about them is NOT true?
(1) Both siRNA and miRNA are processed by DICER.
(2) Both siRNA and-miRNA usually guide silencing of the same genetic loci from which they originate.
(3) miRNA is a natural molecule while siRNA is either natural or a synthetic one.
(4) miRNA, but not siRNA is processed by Drosha.

Introduction

RNA interference (RNAi) is a conserved cellular mechanism mediated by small RNA molecules, primarily small interfering RNA (siRNA) and microRNA (miRNA). Both play crucial roles in post-transcriptional gene regulation but differ in origin, processing, and target specificity. This article clarifies key distinctions between siRNA and miRNA and identifies common misconceptions.

Processing of siRNA and miRNA

• Both siRNA and miRNA are processed by the enzyme Dicer in the cytoplasm, which cleaves precursor RNAs into short double-stranded RNA duplexes (~21–25 nucleotides) that guide gene silencing machinery.

• However, only miRNA precursors are processed by Drosha in the nucleus. Drosha cleaves primary miRNA transcripts (pri-miRNAs) into precursor miRNAs (pre-miRNAs), which are then exported to the cytoplasm for Dicer processing.

• siRNAs typically originate from exogenous or endogenous long double-stranded RNAs and bypass Drosha processing.

Origin and Targeting

• miRNAs are endogenous, naturally occurring molecules transcribed from specific miRNA genes within the genome.

• siRNAs can be natural (e.g., from viruses or transposons) or synthetic, often introduced experimentally for gene silencing.

• siRNAs usually guide silencing of specific target mRNAs with perfect or near-perfect complementarity, often the same locus or exogenous sequences.

• miRNAs typically regulate multiple target mRNAs through imperfect base pairing, affecting genes distinct from their own loci.

Evaluating the Statements

1. Both siRNA and miRNA are processed by Dicer.
   True.

2. Both siRNA and miRNA usually guide silencing of the same genetic loci from which they originate.
   False. siRNAs often target the same locus, but miRNAs generally regulate multiple different mRNAs, not necessarily from their own locus.

3. miRNA is a natural molecule while siRNA is either natural or synthetic.
   True.

4. miRNA, but not siRNA, is processed by Drosha.
   True.

Conclusion

The statement that is NOT true is:
(2) Both siRNA and miRNA usually guide silencing of the same genetic loci from which they originate.