siRNA vs miRNA: 10 Major Differences

siRNA vs miRNA: 17 Major Differences (Updated)

siRNA vs miRNA- There are two types of nucleic acids- DNA and RNA; and are different in terms of structure and function. DNA is double-stranded while RNA is single-stranded, usually.

The DNA is well-known as a unit of inheritance while the RNA is majorly involved in protein synthesis. t-RNA, mRNA and rRNA are three major types of RNA having a function to transfer codon, synthesize protein and provide a site for translation, respectively. 

These three types of RNAs are known to science students but do you know there are other types of RNAs present in a cell as well which perform important functions. 

Those are smaller, mostly single-stranded or double-stranded RNAs that have the power to protect our cells (from the exogenous RNA attacks) and regulate gene expression. 

The smaller, non-coding RNAs have a crucial role in gene silencing and have been involved in the mechanism of gene regulation, popularly known as RNA interference or RNAi. 

RNA interference is a sequence-specific mRNA degradation process that regulates gene expression. Smaller RNAs control the process which is referred to as either miRNA or siRNA. Check out their similarities,

Both follow similar mechanisms to govern genes’ activity.  

Both are processed by the enzyme Dicer in the cytoplasm.

Both are loaded in the RISC ((RNA-induced silencing complex).

Both bind to mRNA, degrade it and abort gene expression. 

Apart from many similarities and involvement in RNA interference, there are significant differences between siRNA and miRNA. In the present article, I will explain to you the most common and important differences between siRNA and miRNA. 

This article will boost your knowledge of RNA interference and the regulation of gene expression.

Stay tuned. 

Differences between siRNA vs miRNA.

Difference between siRNA vs miRNA: 

1. The full name of siRNA is small interfering or short interfering RNA while the full name of miRNA is microRNA. 

2. The siRNA is not conserved between the species while miRNA is highly conserved in the related organisms of species. 

3. Structurally, the siRNA is a 21-23 nucleotide long RNA duplex having a dinucleotide 3’ overhang. Whereas the miRNA is made up of 19-25 nucleotide RNA hairpins which forms duplex by binding with each other.

Pictorial representation of the structural difference between siRNA and miRNA.

4. The siRNA is an exogeneous double-stranded RNA while the miRNA is endogenous and single-stranded. The miRNA forms a duplex by forming the hairpin structure (see the image above).  

Note that both are non-coding RNAs. 

siRNA is usually viral RNA and uptaken by the cell while the miRNA is non-viral RNA or endogenous. 

5. The siRNA is manufactured from the heterochromatin or transposons while the miRNA is manufactured from specific genes. Some genes actually transcribe miRNA which can’t be translated into protein. 

6. As we talked about, the RISC complex process both siRNA and miRNA with a different mechanism of action. 

The siRNA only abort gene expression if it finds the exact complementary sequence on mRNA. On the other side, the miRNA binds imperfectly or at the 3’ untranslated region of the mRNA and abort the translation process. 

Related article: What Is shRNA (Short-hairpin RNA)?  

7. For gene silencing, the siRNA required the Ago 2 protein- argonaute protein 2  whereas the miRNA required the Ago protein only but not necessarily the Ago2. Any argonaute family protein can do miRNA-mediated gene silencing. 

8. Generally, in addition to ago2, several other proteins such as ago1, ago4, ago7 and ago6 are involved in the siRNA-mediated gene silencing in different organisms. Contrary, only ago1 and ago10 are majorly linked in the miRNA-mediated gene regulation. 

‚ÄúSome siRNA binds on the exact complementary mRNA and induce gene silencing by behaving like a miRNA while some miRNA binds to some non-complementary sequences and behave like siRNA.‚Ä̬†

9. Interestingly, previous studies reported significant structural differences between siRNA and miRNA. The siRNA is a single duplex while the miRNA is heteroduplex RNA in structure. 

10. In addition to structural differences, the regulatory targets are different for both too. For instance, the siRNA regulates the expression of different genes while the miRNA regulates the expression of similar types of genes or genes having the same origin. 

Keep in mind that the duo has a direct role in the process of RNA interference but has different effects, targets and modes of action.  

11. The siRNA only do gene silencing by destroying the mRNA while the miRNA do gene silencing by translation repression. 

12. Studies also suggest that the siRNA has involvement not only in gene regulation but also in other epigenetic alterations like histone modification and DNA methylation. On the other side, the miRNA is solely involved in gene regulation only. 

13. So conclusively, the siRNA provides protection agains foreign pathogens and genome stability while the miRNA works as an endogenous gene expression regulator.

The miRNA-mediated gene silencing process.

Besides, all these structural and functional differences, the siRNA and miRNA are present in different organisms too. 

14. The siRNA is not found in all mammals but in lower animals and in plants whereas the miRNA is present in all the animals and plants including higher mammals. 

siRNA and miRNA like smaller RNAs have great values in gene therapy. In the process, an artificial vector transfers the smaller non-coding RNAs into the target genome for target-specific gene silencing.  

15. The siRNA is used in gene therapy and as a therapeutic agent while the miRNA is used as a therapeutic agent, biomarker, drug target and diagnostic tool.  

16. The main function of the siRNA is to maintain genome integrity against foreign RNA molecules while the miRNA works as a regulator of endogenous genes. 

18. A single siRNA binds to single mRNA while the miRNA has multiple action sites of the same as well as different mRNA. More than 100 different target sites are present for a single miRNA molecule. 

Summar in the tabular form:

Full name Small interfering RNAmicroRNA
Site of action Exogenous mRNAEndogenous mRNA
Length 21-23nt19-25nt 
Duplex structure Single duplexheteroduplex
Dinucleotide overhangPresent on the 3’ endAbsent 
Hairpin structureAbsent Present 
Manufactured byHeterochromatin and transposons Active genes 
Requirement Exact complementary sequence on the mRNA3’ untranslated region. 
Binding Perfect Imperfect 
Required proteinAgo2 Any Ago protein 
Mode of action Gene silencing by destroying the mRNAGene silencing by translation repression. 
InvolvementDNA methylation, histone modification and gene regulation Only gene regulation. 
Function Projects agains foreign pathogens and provide genome stability Endogenous gene expression regulator. 
Presence Lower animals and plants Higher animals, other mammals and plant 
Applications Gene therapy and therapeutic agent Therapeutic agent, biomarker, drug target and diagnostic tool  


The RNAi can be used for gene therapy research, artificially synthesized smaller hairpin dsRNA is used for artificial gene silencing called shRNA. The synthetically designed dsRNA is introduced in a cell using the expression vector and using the same mechanism it performs gene silencing.

Scientists now using artificial siRNA which behaves like the endogeneous miRNA for silencing some cancer-causing genes although the success rate is too low. It has potential applications in the treatment of disorders like cancer and infections. 

External sources:

Carthew RW, Sontheimer EJ. Origins and Mechanisms of miRNAs and siRNAs. Cell. 2009;136(4):642-655. doi:10.1016/j.cell.2009.01.035.

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