Regulatory RNAs
What is one way antisense RNA can act as a binding to an mRNA?
RNA
Sense (molecular biology) RNA Sense (molecular biology) Sense (molecular biology) Antisense RNA
Sense_(molecular_biology)-Antisense_RNA RNA-Regulatory_RNAs Sense_(molecular_biology)-Antisense_oligonucleotides Sense_(molecular_biology)-Antisense_DNA Antisense_RNA-Abstract
Antisense RNA is an RNA transcript that is complementary to endogenous mRNA. In other words, it is a non-coding strand complementary to the coding sequence of RNA; this is similar to negative-sense viral RNA. Introducing a transgene coding for antisense RNA is a technique used to block expression of a gene of interest. Radioactively-labelled antisense RNA can be used to show the level of transcription of genes in various cell types. Some alternative antisense structural types are being experimentally applied as antisense therapy, with at least one antisense therapy approved for use in humans. When mRNA forms a duplex with a complementary antisense RNA sequence, translation is blocked. This process is related to RNA interference. Antisense nucleic acid molecules have been used experimentally to bind to mRNA and prevent expression of specific genes. Antisense therapies are also in development; in the USA, the Food and Drug Administration (FDA) has approved phosphorothioate antisense oligos fomivirsen (Vitravene) and mipomersen (Kynamro) for human therapeutic use. Cells can produce antisense RNA molecules naturally, which interact with complementary mRNA molecules and inhibit their expression. 
Several types of RNA can downregulate gene expression by being complementary to a part of an mRNA or a gene's DNA. MicroRNAs (miRNA; 21-22 nt) are found in eukaryotes and act through RNA interference (RNAi), where an effector complex of miRNA and enzymes can cleave complementary mRNA, block the mRNA from being translated, or accelerate its degradation. While small interfering RNAs (siRNA; 20-25 nt) are often produced by breakdown of viral RNA, there are also endogenous sources of siRNAs. siRNAs act through RNA interference in a fashion similar to miRNAs. Some miRNAs and siRNAs can cause genes they target to be methylated, thereby decreasing or increasing transcription of those genes. Animals have Piwi-interacting RNAs (piRNA; 29-30 nt) that are active in germline cells and are thought to be a defense against transposons and play a role in gametogenesis. Many prokaryotes have CRISPR RNAs, a regulatory system similar to RNA interference. Antisense RNAs are widespread; most downregulate a gene, but a few are activators of transcription. One way antisense RNA can act is by binding to an mRNA, forming double-stranded RNA that is enzymatically degraded. There are many long noncoding RNAs that regulate genes in eukaryotes, one such RNA is Xist, which coats one X chromosome in female mammals and inactivates it. An mRNA may contain regulatory elements itself, such as riboswitches, in the 5' untranslated region or 3' untranslated region; these cis-regulatory elements regulate the activity of that mRNA. The untranslated regions can also contain elements that regulate other genes.
Gene silencing can be achieved by introducing into cells a short "antisense oligonucleotide" that is complementary to an RNA target. This experiment was first done by Zamecnik and Stephenson in 1978 and continues to be a useful approach, both for laboratory experiments and potentially for clinical applications (antisense therapy). If the antisense oligonucleotide contains a stretch of DNA or a DNA mimic (phosphorothioate DNA, 2'F-ANA, or others) it can recruit RNase H to degrade the target RNA. This makes the mechanism of gene silencing catalytic. Double-stranded RNA can also act as a catalytic, enzyme-dependent antisense agent through the RNAi/siRNA pathway, involving target mRNA recognition through sense-antisense strand pairing followed by target mRNA degradation by the RNA-induced silencing complex (RISC). The R1 plasmid hok/sok system provides yet another example of an enzyme-dependent antisense regulation process, through enzymatic degradation of the resulting RNA duplex. Other antisense mechanisms are not enzyme-dependent, but involve steric blocking of their target RNA (e.g. to prevent translation or induce alternative splicing). Steric blocking antisense mechanisms often use oligonucleotides that are heavily modified. Since there is no need for RNase H recognition, this can include chemistries such as 2'-O-alkyl, peptide nucleic acid (PNA), locked nucleic acid (LNA), and Morpholino oligomers. 
The two complementary strands of double-stranded DNA (dsDNA) are usually differentiated as the "sense" strand and the "antisense" strand. The DNA sense strand looks like the messenger RNA (mRNA) and can be used to read the expected protein code by human eyes (e.g. ATG codon = Methionine amino acid). However, the DNA sense strand itself is not used to make protein by the cell. It is the DNA antisense strand which serves as the source for the protein code, because, with bases complementary to the DNA sense strand, it is used as a template for the mRNA. Since transcription results in an RNA product complementary to the DNA template strand, the mRNA is complementary to the DNA antisense strand. The mRNA is what is used for translation (protein synthesis). Hence, a base triplet 3'-TAC-5' in the DNA antisense strand can be used as a template which will result in an 5'-AUG-3' base triplet in mRNA (AUG is the codon for Methionine, the start codon). The DNA sense strand will have the triplet ATG which looks just like AUG but "will not be used to make Methionine" because it "will not be used to make mRNA". The DNA sense strand is called a "sense" strand not because it will be used to make protein (it won't be), but because it has a sequence that looks like the protein codon sequence. Students may find this confusing if they misunderstand the meaning of "sense" and if they misunderstand complementation. To make things more confusing, before the convention was set, very early textbooks disagreed on the DNA strands called "sense" and "antisense. "In biology and research, short antisense molecules can interact with complementary strands of nucleic acids, modifying expression of genes. See the section on "antisense oligonucleotides" below. 
Antisense RNA (asRNA) is a single-stranded RNA that is complementary to a messenger RNA (mRNA) strand transcribed within a cell. Some authors have used the term micRNA (mRNA-interfering complementary RNA) to refer to these RNAs but it is not widely used. Antisense RNA may be introduced into a cell to inhibit translation of a complementary mRNA by base pairing to it and physically obstructing the translation machinery. This effect is therefore stoichiometric. An example of naturally occurring mRNA antisense mechanism is the hok/sok system of the "E. coli" R1 plasmid. Antisense RNA has long been thought of as a promising technique for disease therapy; the only such case to have reached the market is the drug fomivirsen. One commentator has characterized antisense RNA as one of "dozens of technologies that are gorgeous in concept, but exasperating in name=DePalma2005></ref> Generally, antisense RNA still lack effective design, biological activity, and efficient route of administration. Historically, the effects of antisense RNA have often been confused with the effects of RNA interference (RNAi), a related process in which "double-stranded" RNA fragments called small interfering RNAs trigger catalytically mediated gene silencing, most typically by targeting the RNA-induced silencing complex (RISC) to bind to and degrade the mRNA. Attempts to genetically engineer transgenic plants to express antisense RNA instead activate the RNAi pathway, although the processes result in differing magnitudes of the same downstream effect; gene silencing. Well-known examples include the Flavr Savr tomato and two cultivars of ringspot-resistant papaya. Transcription of longer "cis"-antisense transcripts is a common phenomenon in the mammalian transcriptome. Although the function of some cases have been described, such as the Zeb2/Sip1 antisense RNA, no general function has been elucidated. In the case of Zeb2/Sip1, the antisense noncoding RNA is opposite the 5' splice site of an intron in the 5'UTR of the Zeb2 mRNA. Expression of the antisense ncRNA prevents splicing of an intron that contains a ribosome entry site necessary for efficient expression of the Zeb2 protein. Transcription of long antisense ncRNAs is often concordant with the associated protein-coding gene, but more detailed studies have revealed that the relative expression patterns of the mRNA and antisense ncRNA are complex. 