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In molecular biology and genetics, the sense of a nucleic acid molecule, particularly of a strand of DNA or RNA, refers to the nature of the roles of the strand and its complement in specifying a sequence of . Depending on the context, sense may have slightly different meanings. For example, the negative-sense strand of DNA is equivalent to the template strand, whereas the positive-sense strand is the non-template strand whose nucleotide sequence is equivalent to the sequence of the mRNA transcript.
Sometimes the phrases coding strand and template strand are encountered in place of sense and antisense, respectively, and in the context of a double-stranded DNA molecule the usage of these terms is essentially equivalent. However, the coding/sense strand need not always contain a code that is used to make a protein; both protein-coding and may be transcribed.
The terms "sense" and "antisense" are relative only to the particular RNA transcript in question, and not to the DNA strand as a whole. In other words, either DNA strand can serve as the sense or antisense strand. Most organisms with sufficiently large genomes make use of both strands, with each strand functioning as the template strand for different RNA transcripts in different places along the same DNA molecule. In some cases, RNA transcripts can be transcribed in both directions (i.e. on either strand) from a common promoter region, or be transcribed from within introns on either strand (see "ambisense" below).
Hence, a base triplet 3′-TAC-5′ in the DNA antisense strand (complementary to the 5′-ATG-3′ of the DNA sense strand) is used as the template which results in a 5′-AUG-3′ base triplet in the mRNA. The DNA sense strand will have the triplet ATG, which looks similar to the mRNA triplet AUG but will not be used to make methionine because it will not be directly 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 corresponds directly to the RNA codon sequence. By this logic, the RNA transcript itself is sometimes described as "sense".
Some regions within a double-stranded DNA molecule code for , which are usually instructions specifying the order in which amino acids are assembled to make proteins, as well as regulatory sequences, RNA splicing sites, non-coding , and other . 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 transcribed DNA strand is called the template strand, with antisense sequence, and the mRNA transcript produced from it is said to be sense sequence (the complement of antisense). The untranscribed DNA strand, complementary to the transcribed strand, is also said to have sense sequence; it has the same sense sequence as the mRNA transcript (though T bases in DNA are substituted with U bases in RNA).
| Used as a template for transcription. |
| Complementary to the template strand. |
| RNA strand that is transcribed from the noncoding (template/antisense) strand. Note1: Except for the fact that all thymines are now uracils (3′CGCTATAGCGTTT 5′), it is complementary to the noncoding (template/antisense) DNA strand and identical to the coding (nontemplate/sense) DNA strand. |
| RNA strand that is transcribed from the coding (nontemplate/sense) strand. Note: Except for the fact that all thymines are now uracils (5′GCGATATCGCAAA 3′), it is complementary to the coding (nontemplate/sense) DNA strand and identical to the noncoding (template/antisense) DNA strand. |
The names assigned to each strand actually depend on which direction you are writing the sequence that contains the information for proteins (the "sense" information), not on which strand is depicted as "on the top" or "on the bottom" (which is arbitrary). The only biological information that is important for labeling strands is the relative locations of the terminal 5′ phosphate group and the terminal 3′ hydroxyl group (at the ends of the strand or sequence in question), because these ends determine the direction of transcription and translation. A sequence written 5′-CGCTAT-3′ is equivalent to a sequence written 3′-TATCGC-5′ as long as the 5′ and 3′ ends are noted. If the ends are not labeled, convention is to assume that both sequences are written in the 5′-to-3′ direction. The "Watson strand" refers to 5′-to-3′ top strand (5′→3′), whereas the "Crick strand" refers to the 5′-to-3′ bottom strand (3′←5′). Both Watson and Crick strands can be either sense or antisense strands depending on the specific gene product made from them.
For example, the notation "YEL021W", an alias of the URA3 gene used in the National Center for Biotechnology Information (NCBI) database, denotes that this gene is in the 21st open reading frame (ORF) from the centromere of the left arm (L) of Yeast (Y) chromosome number V (E), and that the expression coding strand is the Watson strand (W). "YKL074C" denotes the 74th ORF to the left of the centromere of chromosome XI and that the coding strand is the Crick strand (C). Another confusing term referring to "Plus" and "Minus" strand is also widely used. Whether the strand is sense (positive) or antisense (negative), the default query sequence in NCBI BLAST alignment is "Plus" strand.
Some alternative antisense structural types have been experimentally applied as antisense therapy. In the United States, the Food and Drug Administration (FDA) has approved the phosphorothioate antisense oligonucleotides fomivirsen (Vitravene) and mipomersen (Kynamro) for human therapeutic use.
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 to 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.
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