Antisense mRNA
Encyclopedia
Antisense RNA is a single-stranded RNA
that is complementary
to a messenger RNA
(mRNA) strand transcribed
within a cell
. Antisense RNA may be introduced into a cell to inhibit translation
of a complementary mRNA by base pair
ing 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[commercialization] ". 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 RNA
s 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 cultivar
s 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.
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
that is complementary
Complementarity (molecular biology)
In molecular biology, complementarity is a property of double-stranded nucleic acids such as DNA, as well as DNA:RNA duplexes. Each strand is complementary to the other in that the base pairs between them are non-covalently connected via two or three hydrogen bonds...
to a messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
(mRNA) strand transcribed
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...
within a cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
. Antisense RNA may be introduced into a cell to inhibit translation
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
of a complementary mRNA by base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
ing to it and physically obstructing the translation machinery. This effect is therefore stoichiometric
Stoichiometry
Stoichiometry is a branch of chemistry that deals with the relative quantities of reactants and products in chemical reactions. In a balanced chemical reaction, the relations among quantities of reactants and products typically form a ratio of whole numbers...
. An example of naturally occurring mRNA antisense mechanism is the hok/sok system
Hok/sok system
The hok/sok system is a postsegregational killing mechanism employed by the R1 plasmid in Escherichia coli. It was the first type I toxin-antitoxin pair to be identified through characterisation of a plasmid-stabilising locus...
of the E. coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
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
Fomivirsen
Fomivirsen is an antiviral drug. It is used in the treatment of cytomegalovirus retinitis in immunocompromised patients, including those with AIDS...
. One commentator has characterized antisense RNA as one of "dozens of technologies that are gorgeous in concept, but exasperating in
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...
.
Historically, the effects of antisense RNA have often been confused with the effects of RNA interference
RNA interference
RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
(RNAi), a related process in which double-stranded RNA fragments called small interfering RNA
Small interfering RNA
Small interfering RNA , sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA molecules, 20-25 nucleotides in length, that play a variety of roles in biology. The most notable role of siRNA is its involvement in the RNA interference pathway, where it...
s trigger catalytically
Catalysis
Catalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
mediated gene silencing
Gene silencing
Gene silencing is a general term describing epigenetic processes of gene regulation. The term gene silencing is generally used to describe the "switching off" of a gene by a mechanism other than genetic modification...
, most typically by targeting the RNA-induced silencing complex
RNA-induced silencing complex
RNA-Induced Silencing Complex, or RISC, is a multiprotein complex that incorporates one strand of a small interfering RNA or micro RNA . RISC uses the siRNA or miRNA as a template for recognizing complementary mRNA. When it finds a complementary strand, it activates RNase and cleaves the RNA...
(RISC) to bind to and degrade the mRNA. Attempts to genetically engineer
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
transgenic
Transgene
A transgene is a gene or genetic material that has been transferred naturally or by any of a number of genetic engineering techniques from one organism to another....
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
Tomato
The word "tomato" may refer to the plant or the edible, typically red, fruit which it bears. Originating in South America, the tomato was spread around the world following the Spanish colonization of the Americas, and its many varieties are now widely grown, often in greenhouses in cooler...
and two cultivar
Cultivar
A cultivar'Cultivar has two meanings as explained under Formal definition. When used in reference to a taxon, the word does not apply to an individual plant but to all those plants sharing the unique characteristics that define the cultivar. is a plant or group of plants selected for desirable...
s of ringspot
Papaya ringspot virus
Papaya ringspot virus is a plant pathogenic virus in the genus Potyvirus and the virus family Potyviridae.The virus is a non-enveloped, flexous rod-shaped particle that is between 760-800 nm long and 12 nm in diameter. It is transmitted between plants by mechanical activities like...
-resistant papaya
Papaya
The papaya , papaw, or pawpaw is the fruit of the plant Carica papaya, the sole species in the genus Carica of the plant family Caricaceae...
.
Transcription of longer cis-antisense transcripts
Long noncoding RNA
Long non-coding RNAs are generally considered as non-protein coding transcripts longer than 200 nucleotides. This limit is due to practical considerations including the separation of RNAs in common experimental protocols...
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
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
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.