Sense (molecular biology)
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In
molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
and
genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...
, the sense of a nucleic acid molecule, particularly of a strand of DNA or
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
, refers to the nature of the roles of the strand and its
complement A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-clas ...
in specifying a sequence of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s. Depending on the context, sense may have slightly different meanings. For example, 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 In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...
transcript.


DNA sense

Because of the
complementary A complement is something that completes something else. Complement may refer specifically to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class ...
nature of
base-pairing A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
between nucleic acid polymers, a double-stranded DNA molecule will be composed of two strands with sequences that are reverse complements of each other. To help molecular biologists specifically identify each strand individually, the two strands are usually differentiated as the "sense" strand and the "antisense" strand. An individual strand of DNA is referred to as positive-sense (also positive (+) or simply sense) if its
nucleotide sequence A nucleic acid sequence is a succession of bases signified by a series of a set of five different letters that indicate the order of nucleotides forming alleles within a DNA (using GACT) or RNA (GACU) molecule. By convention, sequences are usu ...
corresponds directly to the sequence of an RNA transcript which is
translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
or translatable into a sequence of
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s (provided that any
thymine Thymine () ( symbol T or Thy) is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidi ...
bases in the DNA sequence are replaced with
uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced b ...
bases in the RNA sequence). The other strand of the double-stranded DNA molecule is referred to as negative-sense (also negative (−) or antisense), and is reverse complementary to both the positive-sense strand and the RNA transcript. It is actually the antisense strand that is used as the template from which RNA polymerases construct the RNA transcript, but the complementary base-pairing by which nucleic acid polymerization occurs means that the sequence of the RNA transcript will look identical to the positive-sense strand, apart from the RNA transcript's use of uracil instead of thymine. 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
non-coding RNA A non-coding RNA (ncRNA) is a functional RNA molecule that is not Translation (genetics), translated into a protein. The DNA sequence from which a functional non-coding RNA is transcribed is often called an RNA gene. Abundant and functionally im ...
s 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 An intron is any nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e. a region inside a gene."The notion of the cistron .e., gene ...
on either strand (see "ambisense" below).


Sense DNA

The DNA sense strand looks like the messenger RNA (mRNA) transcript, and can therefore be used to read the expected codon sequence that will ultimately be used during
translation Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
(protein synthesis) to build an amino acid sequence and then a protein. For example, the sequence "ATG" within a DNA sense strand corresponds to an "AUG" codon in the mRNA, which
codes In communications and information processing, code is a system of rules to convert information—such as a letter, word, sound, image, or gesture—into another form, sometimes shortened or secret, for communication through a communication ...
for the amino acid methionine. However, the DNA sense strand itself is not used as the template for the mRNA; it is the DNA antisense strand that 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 Transcription refers to the process of converting sounds (voice, music etc.) into letters or musical notes, or producing a copy of something in another medium, including: Genetics * Transcription (biology), the copying of DNA into RNA, the fir ...
results in an RNA product complementary to the DNA template strand, the mRNA is complementary to the DNA antisense strand. 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".


Example with double-stranded DNA

:''DNA strand 1: antisense strand'' (transcribed to) → ''RNA strand (sense)'' :''DNA strand 2: sense strand'' Some regions within a double-stranded DNA molecule code for
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
s, which are usually instructions specifying the order in which amino acids are assembled to make proteins, as well as regulatory sequences, splicing sites, non-coding introns, and other
gene product A gene product is the biochemical material, either RNA or protein, resulting from expression of a gene. A measurement of the amount of gene product is sometimes used to infer how active a gene is. Abnormal amounts of gene product can be correlate ...
s. 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 Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
. 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). 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 The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The ...
(NCBI) database, denotes that this gene is in the 21st
open reading frame In molecular biology, open reading frames (ORFs) are defined as spans of DNA sequence between the start and stop codons. Usually, this is considered within a studied region of a prokaryotic DNA sequence, where only one of the six possible readin ...
(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.


Ambisense

A single-stranded genome that is used in both positive-sense and negative-sense capacities is said to be ambisense. Some viruses have ambisense genomes. Bunyaviruses have three single-stranded RNA (ssRNA) fragments, some of them containing both positive-sense and negative-sense sections;
arenavirus An arenavirus is a bisegmented ambisense RNA virus that is a member of the family ''Arenaviridae''. These viruses infect rodents and occasionally humans. A class of novel, highly divergent arenaviruses, properly known as reptarenaviruses, have ...
es are also ssRNA viruses with an ambisense genome, as they have three fragments that are mainly negative-sense except for part of the 5′ ends of the large and small segments of their genome.


Antisense RNA

An RNA sequence that is complementary to an endogenous mRNA transcript is sometimes called " antisense RNA". In other words, it is a non-coding strand complementary to the coding sequence of RNA; this is similar to negative-sense viral RNA. When mRNA forms a duplex with a complementary antisense RNA sequence, translation is blocked. This process is related to
RNA interference RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...
. Cells can produce antisense RNA molecules naturally, called
microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. mi ...
s, which interact with complementary mRNA molecules and inhibit their
expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, o ...
. The concept has also been exploited as a molecular biology technique, by artificially introducing a
transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change th ...
coding for antisense RNA in order to block the expression of a gene of interest. Radioactively or fluorescently labelled antisense RNA can be used to show the level of transcription of genes in various cell types. Some alternative antisense structural types have been experimentally applied as
antisense therapy Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre- ...
. In the United States, the
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) has approved the phosphorothioate antisense oligonucleotides
fomivirsen Fomivirsen (brand name Vitravene) is an antisense antiviral drug that was used in the treatment of cytomegalovirus retinitis (CMV) in immunocompromised patients, including those with AIDS. It was administered via intraocular injection. It was d ...
(Vitravene) and mipomersen (Kynamro) for human therapeutic use.


RNA sense in viruses

In
virology Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, th ...
, the term "sense" has a slightly different meaning. The genome of an 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 terms such as "positive-strand" equivalent to "positive-sense", and "plus-strand" equivalent to "plus-sense". Whether a viral genome is positive-sense or negative-sense can be used as a basis for classifying viruses.


Positive-sense

Positive-sense ( 5′-to- 3′) viral RNA signifies that a particular viral RNA sequence may be directly
translated Translation is the communication of the meaning of a source-language text by means of an equivalent target-language text. The English language draws a terminological distinction (which does not exist in every language) between ''transla ...
into viral proteins (e.g., those needed for viral replication). 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 ''Coronaviridae'' is a family of enveloped, positive-strand RNA viruses which infect amphibians, birds, and mammals. The group includes the subfamilies '' Letovirinae'' and ''Orthocoronavirinae;'' the members of the latter are known as coronavi ...
) have positive-sense genomes that can act as mRNA and be used directly to synthesize proteins without the help of a complementary RNA intermediate. Because of this, these viruses do not need to have an RNA polymerase packaged into the
virion A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's ...
—the RNA polymerase will be one of the first proteins produced by the host cell, since it is needed in order for the virus's genome to be replicated.


Negative-sense

Negative-sense (3′-to-5′) viral RNA is complementary to the viral mRNA, thus a positive-sense RNA must be produced by an RNA-dependent RNA polymerase from it prior to translation. Like DNA, negative-sense RNA has a nucleotide sequence complementary to the mRNA that it encodes; also like DNA, this RNA cannot be translated into protein directly. Instead, it must first be transcribed into a positive-sense RNA that acts as an mRNA. Some viruses (e.g. influenza viruses) have negative-sense genomes and so must carry an RNA polymerase inside the virion.


Antisense oligonucleotides

Gene silencing Gene silencing is the regulation of gene expression in a cell to prevent the expression of a certain gene. Gene silencing can occur during either transcription or translation and is often used in research. In particular, methods used to silence ge ...
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 Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre- ...
). Several viruses, such as influenza viruses Respiratory syncytial virus (RSV) and
SARS coronavirus Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for th ...
(SARS-CoV), have been targeted using antisense oligonucleotides to inhibit their replication in host cells. 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 Ribonuclease H (abbreviated RNase H or RNH) is a family of non-sequence-specific endonuclease enzymes that catalyze the cleavage of RNA in an RNA/ DNA substrate via a hydrolytic mechanism. Members of the RNase H family can be found in nearly ...
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 RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by ...
/
siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating ...
pathway, involving target mRNA recognition through sense-antisense strand pairing followed by target mRNA degradation by the
RNA-induced silencing complex The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA ...
(RISC). The R1 plasmid
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. It is a type I ...
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 Peptide nucleic acid (PNA) is an artificially synthesized polymer similar to DNA or RNA. Synthetic peptide nucleic acid oligomers have been used in recent years in molecular biology procedures, diagnostic assays, and antisense therapies. Due ...
(PNA),
locked nucleic acid A locked nucleic acid (LNA), also known as bridged nucleic acid (BNA), and often referred to as inaccessible RNA, is a modified RNA nucleotide in which the ribose moiety is modified with an extra bridge connecting the 2' oxygen and 4' carbon. Th ...
(LNA), and
Morpholino A Morpholino, also known as a Morpholino oligomer and as a phosphorodiamidate Morpholino oligomer (PMO), is a type of oligomer molecule (colloquially, an oligo) used in molecular biology to modify gene expression. Its molecular structure contain ...
oligomers.


See also

*
Antisense therapy Antisense therapy is a form of treatment that uses antisense oligonucleotides (ASOs) to target messenger RNA (mRNA). ASOs are capable of altering mRNA expression through a variety of mechanisms, including ribonuclease H mediated decay of the pre- ...
*
Directionality (molecular biology) Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. In a single strand of DNA or RNA, the chemical convention of naming carbon atoms in the nucleotide pentose-sugar-r ...
* DNA codon table * RNA virus *
Transcription (genetics) Transcription is the process of copying a segment of DNA into RNA. The segments of DNA transcribed into RNA molecules that can encode proteins are said to produce messenger RNA (mRNA). Other segments of DNA are copied into RNA molecules calle ...
*
Translation (genetics) In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or endoplasmic reticulum synthesize proteins after the process of transcription of DNA to RNA in the cell's nucleus. The entire process ...
*
Viral replication Viral replication is the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. Through the generation of abundant copies of its genome an ...


References

{{DEFAULTSORT:Sense (Molecular Biology) DNA Molecular biology RNA Virology