The RNA is a ribonucleic acid which is different from the DNA. Different RNA molecules are present in our cells for performing different functions.
Three major types of RNA are involved in protein translation. The tRNA transfer codon, the mRNA passes messages for creating protein and the rRNA facilitates site for translation.
In addition to these three major types of RNA, several different types of smaller RNAs are also present in a cell which protects the cell from the exogenous RNA attacks and helps in the gene regulation.
These smaller, non-coding RNAs are major constituents of gene silencing and involved in the mechanism of gene regulation called RNA interference or RNAi.
RNA interference is a sequence-specific mRNA degradation process which regulates gene expression. The RNA interference is mediated by the smaller RNA molecules called miRNA or siRNA.
Both types of smaller RNA molecules mediates gene regulation using the same mechanism.
Both are processed by the enzyme dicer in the cytoplasm, loaded in the RISC ( RNA induced silencing complex).
By binding with the target mRNA, it degrades mRNA or aborts the gene expression.
Though both are involved in the RNA interference mechanism and works almost similarly, there are some differences between both the molecules.
In the present article, we will discuss 10 of those major differences between siRNA and miRNA.
Difference between siRNA vs miRNA:
2. The siRNA is not conserved throughout the species while miRNA are 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 to 19-25 nucleotide RNA hairpin which forms duplex by binding with each other.
4. The siRNA is an exogeneous double-stranded RNA uptaken by the cell, generally, are viral RNAs, it is also encoded by heterochromatin regions and transposons.
Whereas the miRNA are endogenous single-stranded, non-coding RNA molecule, by forming a hairpin structure, it becomes duplex. The miRNAs are the non-coding RNA molecule which is encoded by some of the genes.
5. Though both are processed by the RISC, 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 hinder in the translation process.
Read further: RNA Interference (RNAi): A Process Of Gene silencing.
6. For doing gene silencing, the siRNA required the Ago 2 protein- argonaute protein 2 whereas the miRNA required the Ago protein but not necessarily the Ago2. Any argonaute family protein can do miRNA mediated gene silencing.
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, ago1 and ago10 are majorly linked in the miRNA mediated gene regulation.
“Some 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.”
7. Interestingly, one of the structural differences between both type of RNA is the duplex structure, the miRNA has a heteroduplex structure while the siRNA is a single duplex structure.
The siRNA and miRNA both involved in the gene regulation but the nature of the regulatory target is different. The siRNA regulates different gens while the miRNA does silencing of the similar genes from which they originate.
The main function of the RNA interference is to abort the gene expression, however, different molecules have different effects.
8. For example, the siRNA cleaves the mDNA by binding to the complementary sequences while the miRNA binds to untranslated regions of the mRNA and do the translation repression as well as the mRNA cleavage.
In addition to this, the siRNA is also involved in other epigenetic regulations such as histone modification and DNA methylation.
9. The significance of the siRNA is to provide viral defence and genome stability while the miRNA functions as endogeneous gene expression regulator.
10. The siRNA is not found in mammals but present in lower animal and plant kingdoms whereas the miRNA are present in all the animal and plant.
The smaller dsRNA molecules have great importance in gene therapy. The siRNA is used as a therapeutic agent.
Using the artificial vector, smaller non-coding RNAs are inserted into the genome complementary to the mRNA target of our interest.
Whereas the miRNA is used as a therapeutic agent, drug target and diagnostic tool. Furthermore, it is also used as a biomarker.
The main function of the siRNA is to maintain genome integrity against foreign RNA molecules while the miRNA works as regulators of endogenous genes.
A single siRNA binds to single mRNA while the miRNA have multiple action sites of same as well as different mRNA. More than 100 different target sites are present for a single miRNA molecule.
The RNAi can be used for gene therapy research, artificially synthesised smaller hairpin dsRNA are 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.
Scientist now using artificial siRNA which behaves like the endogeneous miRNA for silencing of some cancer-causing genes although the success rate is too low.