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 :)
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.
