Difference Between miRNA and siRNA

Main Difference – miRNA vs siRNA

miRNA and siRNA are two types of non-coding RNA which are involved in the gene regulation. They also serve as a novel class of therapeutic agents in the treatments of cancers and infections. Both miRNA and siRNA are short, duplex RNA molecules, exerting gene silencing effects by targeting messenger RNA (mRNA) at the posttranscriptional level. Though their function is similar in gene silencing, mechanisms of action and clinical applications are different from each other. The main difference between miRNA and siRNA is that miRNA can act upon multiple mRNA targets, but siRNA acts upon only a single mRNA target, which is very specific to the type of siRNA. Thus, the therapeutic approaches of miRNA and siRNA are also different to each other.

Key Areas Covered

1. What is miRNA
      – Definition, Features, Function
2. What is siRNA
      – Definition, Features, Function
3. What are the Similarities Between miRNA and siRNA
      – Outline of Common Features
4. What is the Difference Between miRNA and siRNA
      – Comparison of Key Differences

Key Terms: AGO2, Dicer, Gene Silencing, MicroRNA (miRNA), pri-miRNA, RISC, RNA Interference (RNAi), Small Interfering RNA (siRNA)

What is miRNA

The microRNA (miRNA) is a short, single-stranded RNA molecule, comprising of 19-25 nucleotides. The first miRNA was discovered in C. Elegans in 1993. miRNA is a class of small interfering RNA, which inhibits the gene expression at the post-transcriptional level. The transcription of miRNA genes is done by RNA polymerase to, produce primary miRNA (pri-miRNA). The pri-miRNA is 5’ capped, polyadenylated at its 3’ end, and it forms a double-stranded stem loop structure. These pri-miRNA molecules are cleaved by a microprocessor complex, forming the precursor miRNA (pre-miRNA). The duplex molecules of pre-miRNA comprise 70-100 nucleotides. Exportin 5 protein transports the pre-miRNA molecules into the cytoplasm from the nucleus for further processing into miRNA by Dicer proteins. Hence, miRNA is a RNA duplex, comprising of 18-25 nucleotides. Dicer proteins are a specialized type of RNase III-like enzyme.

Figure 1: The formation and function of miRNA

The association of miRNA with the RNA-induced silencing complex (RISC) protein forms a complex called miRISC. The sense strand of the miRNA is released at the miRISC complex. Then, mRNAs with the complementary sequences to the antisense RNA strand in the miRISC complex are selected by partial complementary base pairing. This binding of miRISC complex with the target mRNA may repress the translation, degrade the mRNA molecule or cleave the mRNA molecule.

What is siRNA

The small interfering RNA (siRNA) is the another type of short, duplex RNA, which silences the gene expression by cleaving the mRNA. The siRNA was also first discovered in C. Elegans in a process called RNA interference (RNAi) of effective gene inhibition by exogenous RNA. Double-stranded RNA (dsRNA) molecules can be generated inside the cell by transcription of cellular genes, infecting pathogens or artificial introduction. This dsRNA is cleaved by Dicer proteins into small dsRNAs known as siRNA. These siRNAs are 21-23 nucleotides long with two nucleotides overhangs at the 3’ end. The siRNA in the cytoplasm is associated with RISC proteins and the sense strand of the siRNA molecule is cleaved by an endonuclease called argonaute 2 (AGO2) component of the RISC. The relevant mRNA molecule is recognized by the antisense RNA strand of the siRNA, which is still attached to the RISC protein. The cleavage of the target mRNA molecule is done by the AGO2 component.

Figure 2: Gene silencing by siRNA

Since siRNA can only target a specific mRNA molecule, a specific silencing of gene expression can be achieved by the siRNA. Furthermore, since siRNA is naturally absent in mammals, it can be used as a specific therapeutic agent.

Similarities Between miRNA and siRNA

Both miRNA and siRNA are short, duplex RNA molecules.
Both miRNA and siRNA are types of non-coding RNA involved in the gene regulation
Both types of RNA exerts gene silencing effects by targeting messenger RNA at the posttranscriptional level.
Both serve as a novel class of therapeutic agents in the treatments of cancers and infections.

Definition

miRNA: The miRNA is a short segment of RNA which suppresses the gene expression by binding to the complementary segments of messenger RNA.

siRNA: The siRNA is a short segment of RNA which operates in the RNA interference (RNAi) pathway.

Occurrence

miRNA: The miRNA is found in animals and plants.

siRNA: The siRNA is found in lower animals and plants, but not in mammals.

Structure

miRNA: miRNA is a 18-25 nucleotides long single-stranded molecule with two nucleotides overhung at the 3’ end.

siRNA: siRNA is a 21-23 nucleotides long duplex molecule with two nucleotides overhang at the 3’ end.

Prior to Dicer Processing

miRNA: Prior to the dicer processing, miRNA is in its precursor miRNA form, containing 70-100 nucleotides with scattered mismatches. The pre-miRNA exists in a hairpin loop structure.

siRNA: Prior to dicer processing, siRNA is a double-stranded RNA molecule, containing 30-100 nucleotides.

Complementariness

miRNA: The miRNA is partially complementary to the mRNA. It mainly targets the untranslated regions of the miRNA.

siRNA: The siRNA is fully complementary to the target mRNA.

Number of mRNA Targets

miRNA: The miRNA is capable of targeting over 100 of mRNA types at the same time.

siRNA: The siRNA is capable of targeting only one mRNA type.

Mechanism of Gene Regulation

miRNA: The miRNA repress the translation by degradation of mRNA. The endonucleolytic cleavage rarely occurs in miRNA when a high rate of complementarity is found in the target.

siRNA: The siRNA regulates gene expression by endonucleolytic cleavage.

Regulation

miRNA: The miRNA regulates the same genes from which the miRNA is transcribed as well as many other genes.

siRNA: The siRNA only regulates the genes from which the siRNA is transcribed.

Clinical Applications

miRNA: The miRNA serves as a drug target, therapeutic agent or diagnostic and biomarker tool.

siRNA: The siRNA serves as a therapeutic agent.

Conclusion

The miRNA and siRNA are the two types of non-coding RNA, which are involved in the regulation of gene expression. Both miRNA and siRNA are double-stranded RNA moleules. Both types of RNA undergo similar mechanisms of gene silencing by a process known as RNA interference. However, miRNA is capable of targeting many types of RNA since the sequence of miRNA is complementary to the untranslated regions of an mRNA. On the other hand, siRNA is capable of targeting only a selected type of mRNA. Therefore, the main difference between miRNA and siRNA is the specificity of each RNA type in RNA interference.

Reference:

1. “MiRNA (microRNA) Introduction.” Sigma-Aldrich. N.p., n.d. Web. Available here. 24 July 2017.
2. “SiRNA Applications.” Applications – siRNA | GE Dharmacon. N.p., n.d. Web. Available here. 24 July 2017.
3. “SiRNA Versus miRNA as Therapeutics for Gene Silencing.” ScienceDirect. N.p., n.d. Web. Available here. 24 July 2017.

Image Courtesy:

1. “MiRNA” By Kelvinsong – Own work (CC BY 3.0) via Commons Wikimedia
2. “SiRNA mechanism.2” By Singh135 – Own work (CC BY-SA 4.0) via Commons Wikimedia