RNA Synthesis & Modifications—Differences between miRNA and siRNA

What are the differences between miRNA and siRNA?

MicroRNA (miRNA) and small interfering RNA (siRNA) are both short, non-coding RNA molecules involved in post-transcriptional gene regulation. Despite their similarities, they differ in origin, mechanism, and application.

	miRNA	siRNA
Origin	Endogenously encoded; processed from primary miRNA (pri-miRNA) to mature miRNA.	Often exogenous (synthetic or viral); processed from long double-stranded RNA (dsRNA).
Structure	Single-stranded with imperfectly paired hairpin structures.	Double-stranded RNA with perfect complementarity.
Mechanism of Action	Binds to partially complementary sequences in the 3' UTR of mRNA, leading to translational repression or degradation.	Binds to perfectly complementary sequences, inducing target mRNA cleavage and degradation.
Target Specificity	Broad target range; regulates multiple genes due to partial complementarity.	Highly specific; targets a single mRNA due to perfect base pairing.
Biological Function	Regulates endogenous gene expression; involved in development, cell differentiation, and stress responses.	Acts as a defense mechanism against viruses and transposable elements.
Applications	Biomarkers for disease diagnostics and prognostics; potential for modulating multiple pathways in therapy.	Research tools for gene silencing; therapeutics for precise gene targeting (e.g., ONPATTRO).

While both miRNA and siRNA are crucial players in RNA interference, they differ significantly in their origin, targeting mechanisms, and functional roles. miRNAs are endogenous regulators with broader, less specific effects, whereas siRNAs are more specific tools for precise gene silencing, making them complementary in research and therapeutic applications.

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