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From what I understand, microRNA binds to proteins which can cut certain mRNA strands do that this protein is not synthesised. This seems like gene silencing to me, however I have also come across the term siRNA and antisense RNA...

Would be grateful if someone could explain what these are and how they work, and perhaps how they can be applied to treating diseases... Thank you in advance :)

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  • $\begingroup$ Can you please clarify your question? At the moment it is hard to understand. $\endgroup$ – Chris Mar 11 '15 at 14:21
  • $\begingroup$ @Chris I am looking for a description of the functions of microRNA, siRNA and antisense RNA and how they carry out these functions. Also, if possible, how they can be applied to treating diseases. I have heard, for example, of microRNA being used to treat cancer, but I don't understand how... $\endgroup$ – 21joanna12 Mar 11 '15 at 14:27
  • $\begingroup$ I have edited your question slightly to replace "bones" with "binds". If this was not what you meant, please revert the edit. $\endgroup$ – user137 Mar 11 '15 at 14:50
  • $\begingroup$ Is this from homework or for a class? $\endgroup$ – Atl LED Mar 11 '15 at 19:10
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    $\begingroup$ There is an entire review on this. Your question is too broad as of now. $\endgroup$ – WYSIWYG Mar 11 '15 at 21:10
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MicroRNA (miRNA) are gene-regulatory RNAs that are loaded onto the RNA-induced silencing complex (RISC) and interact with partially-complementary targets on mRNA to suppress protein expression. The miRNA is originally double-stranded and composed of strands about 21 nucleotides long; on loading onto RISC, one strand is degraded and the other, the "guide" strand, is held on the surface of RISC where it can interact with mRNA. The targets recognized by the guide strand are most commonly on the 3'-untranslated region (UTR) of an RNA. Binding can suppress assembly of an initiation complex on the 5' cap of an mRNA because the mRNA is bound into a circular shape at the initiation of translation, bringing the 3'-UTR and 5'-UTR close together.

If the RISC loads an RNA than then finds a perfectly complementary target, RISC cleaves the target RNA using the activity of one of the protein components of RISC called Argonaute. This property is exploited experimentally by manufacturing small interfering RNAs (siRNA) intentionally targeted to particular target sequences. Once loaded into RISC these siRNA might recognize and cleave their perfectly complementary target sequence within an mRNA (though there is a significant failure rate, so several sequences are often tried). The siRNA will also have miRNA-like effects on some partially-complementary targets on various mRNAs, leading to the observation that a single siRNA sequence can modulate expression of hundreds of off-target genes.

Antisense is a nucleic acid strand (or nucleic acid analog) that is complementary to an mRNA sequence. Antisense occurs naturally and can trigger RNA degradation by the action of the enzyme RNase H. Originally natural antisense RNA was tried as a method for silencing a gene, but the poor stability of RNA in cells led to development of nucleic acid analogs that are more nuclease resistant and still activate RNase H (such as phosphorothioate RNA) and other nucleic acid analogs that bind to RNA and sterically inhibit processes without activating RNase H (such as 2'-O-methyl phosphorothioate RNA, Morpholino oligos, locked nucleic acids, or peptide nucleic acids). These latter RNase-H independent oligos do not trigger degradation of mRNA but they can be used like molecular masking tape to block translation, alter splicing of pre-mRNA, inhibit activity of miRNA, block ribozyme activity, and interfere with various other processes that require some other factor to bind to a particular sequence on an RNA molecule.

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  • $\begingroup$ Thank you for your reply! So it seems to me like the siRNA is just like microRNA, but we make it ourselves rather than it being a natural cell process like how microRNA is used? And also, is the microRNA code on an intron? $\endgroup$ – 21joanna12 Mar 11 '15 at 17:05
  • $\begingroup$ I have looked up more about siRNA and see that mmicroRNA does not have to be 100% specific, but siRNA does. Therefore siRNA only leads to cleavage of the mRNA strand from which it came (so it is complementary to this). Dooes this mean that siRNA is likely to be coded for on an intron in a gene? Also, I have read that microRNA 'inhibits translation of mRNA' and siRNA 'cleaves mRNA', so it seems like they work in two different ways (this is from a website comparing miRNA and siRNA). Could you elaborate on how exactly each works? $\endgroup$ – 21joanna12 Mar 11 '15 at 19:12
  • $\begingroup$ In some cases, miRNAs are clipped out of introns. These miRNAs are sometimes called miRtrons. en.wikipedia.org/wiki/Mirtron The mRNA cleavage and the translational inhibition are both mediated by the RISC, using the miRNA as its target-recognition moiety. The cleavage activity is catalyzed by Argonaute, one of the protein components of RISC. en.wikipedia.org/wiki/Argonaute $\endgroup$ – Jon D. Moulton Mar 12 '15 at 14:55

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