Sense (molecular biology)

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Sense, when applied in a molecular biology context, is a general concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules. Depending on the context within molecular biology, sense may have slightly different meanings.

DNA sense

Molecular biologists call a DNA single strand or sequence sense (or positive sense) if an RNA version of the same sequence is translated or translatable into protein, and they call its complement antisense (or negative sense). Sometimes the phrase coding strand is encountered however, protein coding and non-coding RNA's can be transcribed similarly from both strands, in some cases being transcribed in both directions from a common promoter region, or being transcribed from within introns, on both strands.

Antisense DNA

Schematic showing how antisense DNA strands can interfere with protein translation.

Antisense molecules interact with complementary strands of nucleic acids, modifying expression of genes.

Some regions within a double strand of DNA code for genes, which are usually instructions specifying the order of amino acids in a protein along with regulatory sequences, splicing sites, noncoding introns and other complicating details. For a cell to use this information, one strand of the DNA serves as a template for the synthesis of a complementary strand of RNA. The template DNA strand is called the transcribed strand with antisense sequence and the mRNA transcript is said to be sense sequence (the complement of antisense). Because the DNA is double-stranded, the strand complementary to the antisense sequence is called non-transcribed strand and has the same sense sequence as the mRNA transcript (though T bases in DNA are substituted with U bases in RNA).

DNA strand 1: sense strand

DNA strand 2: antisense strand (copied to)→ RNA strand (sense)

Many forms of antisense have been developed and can be broadly categorized into enzyme-dependent antisense or steric blocking antisense.

Enzyme-dependent antisense includes forms dependent on RNase H activity to degrade target mRNA, including single-stranded DNA, RNA, and phosphorothioate antisense. The R1 plasmid hok/sok system is an example of mRNA antisense regulation process, through enzymatic degradation of the resulting RNA duplex. Double stranded RNA acts as enzyme-dependent antisense 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).

Steric blocking antisense (RNase-H independent antisense)[1] interferes with gene expression or other mRNA-dependent cellular processes by binding to a target sequence of mRNA and getting in the way of other processes. Steric blocking antisense includes 2'-O alkyl (usually in chimeras with RNase-H dependent antisense), peptide nucleic acid (PNA), locked nucleic acid (LNA) and Morpholino antisense.

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 a phosphorothioate antisense oligo, fomivirsen (Vitravene), for human therapeutic use.

Cells can produce antisense RNA molecules naturally, which interact with complementary mRNA molecules and inhibit their expression.

Ambisense

A genome which contains both positive-sense and negative-sense is said to be ambisense. Bunya viruses have 3 fragments containing both positive-sense and negative-sense sections; arenaviruses are also ambisense, having 2 fragments which are mainly negative-sense except for part of the 5' ends of the large and small segments of their genome.

Antisense mRNA

Antisense mRNA is an mRNA transcript that is complementary to endogenous mRNA. In other words, it is a non-coding strand complementary to the coding sequence of mRNA; this is similar to negative-sense viral RNA. Introducing a transgene coding for antisense mRNA is a technique used to block expression of a gene of interest. Radioactively-labelled antisense mRNA 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.

RNA sense

In virology, the genome of a RNA virus can be said to be either positive-sense, also known as a "plus-strand", or negative-sense, also known as a "minus-strand". In most cases, the terms sense and strand are used interchangeably, making such terms as positive-strand equivalent to positive-sense, and plus-strand equivalent to plus-sense. Whether a virus is positive-sense or negative-sense can be used as a basis for classifiying viruses.

Positive-sense

Positive-sense (5' to 3') viral RNA signifies that a particular viral RNA sequence may be directly translated into the desired viral proteins. Therefore, in positive-sense RNA viruses, the viral RNA genome can be considered viral mRNA, and can be immediately translated by the host cell. Unlike negative-sense RNA, positive-sense RNA is of the same sense as mRNA. Some viruses (e.g. Coronaviridae) have positive-sense genomes which can act as mRNA and be used directly to synthesise proteins without the help of a complementary RNA intermediate. Because of this, these viruses do not need to have an RNA transcriptase packaged into the virion.

Negative-sense

Negative-sense (3' to 5') viral RNA is complementary to the viral mRNA and thus must be converted to positive-sense RNA by an RNA polymerase prior to translation. Negative-sense RNA (like DNA) has a nucleotide sequence complementary to the mRNA that it encodes. Like DNA, this RNA cannot be translated into protein directly. Instead, it must first be transcribed into a positive-sense RNA which acts as an mRNA. Some viruses (Influenza, for example) have negative-sense genomes and so must carry an RNA polymerase inside the virion.

See also

References


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