Sense (molecular biology)
Encyclopedia
In molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

 and genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

, sense is a concept used to compare the polarity of nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

 molecules, such as DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 or RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

, to other nucleic acid molecules. Depending on the context within molecular biology, sense may have slightly different meanings.

DNA sense

Molecular biologists
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

 call a single strand of DNA sense (or positive (+) sense) if an RNA version of the same sequence is translated or translatable into protein. Its complementary strand
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...

 is called antisense (or negative (-) sense). Sometimes the phrase coding strand is encountered; however, protein coding and non-coding RNA
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...

'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 (see "ambisense" below).

Antisense DNA

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
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) 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
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...

 strands of nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...

s, modifying expression of genes
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. See: siRNA
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...

.

Example with double-stranded DNA

DNA strand 1: antisense strand (copied to)→ RNA strand (sense)

DNA strand 2: sense strand

Some regions within a double strand of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 code for genes, which are usually instructions specifying the order of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s in a protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 along with regulatory sequences, splicing
RNA splicing
In molecular biology and genetics, splicing is a modification of an RNA after transcription, in which introns are removed and exons are joined. This is needed for the typical eukaryotic messenger RNA before it can be used to produce a correct protein through translation...

 sites, noncoding 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...

s, 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
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

. 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).
5'CGCTATAGCGTTTCAT 3' DNA antisense strand (template/noncoding), Watson strand Used as a template for transcription.
3'GCGATATCGCAAAGTA 5' DNA sense strand (nontemplate/coding), Crick strand Complementary to the template strand.
3'GCGAUAUCGCAAAGUA 5' mRNA Sense transcript RNA strand that is transcribed from the noncoding (template/antisense) strand. Note1: Except for the fact that all thymines are now uracils (T-->U), it is complementary to the noncoding (template/antisense) DNA strand (identical to the coding (nontemplate/sense) DNA strand). Note2 There is an AUG start codon at the 5' end (although written backwards here).
5'CGCUAUAGCGUUUCAU 3' mRNA Antisense transcript RNA strand that is transcribed from the coding (nontemplate/sense) strand. Note: Except for the fact that all thymines are now uracils (T-->U), it is complementary to the coding (nontemplate/sense) DNA strand (identical to the noncoding (template/antisense) DNA strand.


A note on the confusion between "sense" and "antisense" strands: The strand names actually depend on which direction you are writing the sequence that contains the information for proteins (the "sense" information), not on which strand is on the top or bottom (that is arbitrary). The only real biological information that is important for labeling strands is the location of the 5' phosphate group and the 3' hydroxyl group because these ends determine the direction of transcription and translation. A sequence 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 the sequence is written in the 5' to 3' direction. Good rule of thumb for figuring out the "sense" strand: Look for the start codon ATG (AUG in mRNA). In the table example, the sense mRNA has the AUG codon at the end (remember that translation proceeds in the 5' to 3' direction).

Ambisense

A single-stranded genome that contains both positive-sense and negative-sense is said to be ambisense.
Bunya viruses
Bunyaviridae
Bunyaviridae is a family of negative-stranded RNA viruses. Though generally found in arthropods or rodents, certain viruses in this family occasionally infect humans. Some of them also infect plants....

 have 3 single-stranded RNA (ssRNA) fragments containing both positive-sense and negative-sense sections; arenavirus
Arenavirus
Arenavirus is a genus of virus that infects rodents and occasionally humans. At least eight Arenaviruses are known to cause human disease. The diseases derived from Arenaviruses range in severity. Aseptic meningitis, a severe human disease that causes inflammation covering the brain and spinal...

es are also ssRNA viruses with an ambisense genome, as they have 2 fragments that are mainly negative-sense except for part of the 5' ends of the large and small segments of their genome.

Antisense RNA

Antisense RNA is an RNA transcript that is complementary to endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 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
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....

 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
Nucleic acid analogues
Nucleic acid analogues are compounds structurally similar to naturally occurring RNA and DNA, used in medicine and in molecular biology research....

 are being experimentally applied as antisense therapy
Antisense therapy
Antisense therapy is a form of treatment for genetic disorders or infections.When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nuc acid that will bind to the messenger RNA produced by that gene and inactivate...

, 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 called 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...

.

Antisense nucleic acid molecules have been used experimentally to bind to mRNA and prevent expression of specific genes. Antisense therapies
Antisense therapy
Antisense therapy is a form of treatment for genetic disorders or infections.When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nuc acid that will bind to the messenger RNA produced by that gene and inactivate...

 are also in development; in the USA, the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 (FDA) has approved a phosphorothioate antisense oligo, fomivirsen
Fomivirsen
Fomivirsen is an antiviral drug. It is used in the treatment of cytomegalovirus retinitis in immunocompromised patients, including those with AIDS...

 (Vitravene), for human therapeutic use.

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

RNA sense in viruses

In virology
Virology
Virology is the study of viruses and virus-like agents: their structure, classification and evolution, their ways to infect and exploit cells for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy...

, the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 of an RNA virus
RNA virus
An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

 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 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 (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...

 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
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 is of the same sense as mRNA. Some viruses (e.g., Coronaviridae
Coronaviridae
Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses with club-shaped surface about 120-160 nm in diameter that resemble a “corona”.-Virology:...

) 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.

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
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

 prior to translation. Negative-sense RNA (like DNA) has a nucleotide sequence complementary to the mRNA that it encodes. Like DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

, this RNA cannot be translated into protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 directly. Instead, it must first be transcribed into a positive-sense RNA that acts as an mRNA. Some viruses (Influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

, for example) have negative-sense genomes and so must carry an RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

 inside the virion. Shut up Will.

Enzymes

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
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...

 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
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...

/siRNA
Sírna
Sírna Sáeglach , son of Dian mac Demal, son of Demal mac Rothechtaid, son of Rothechtaid mac Main, was, according to medieval Irish legend and historical tradition, a High King of Ireland...

 pathway, involving target mRNA recognition through sense-antisense strand pairing followed by target mRNA degradation by 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).

Steric blocking antisense (RNase-H-independent antisense)http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10807004&query_hl=12 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
Locked nucleic acid
A locked nucleic acid , often referred to as inaccessible RNA, is a modified RNA nucleotide. The ribose moiety of an LNA nucleotide is modified with an extra bridge connecting the 2' oxygen and 4' carbon. The bridge "locks" the ribose in the 3'-endo conformation, which is often found in the A-form...

 (LNA), and Morpholino
Morpholino
In molecular biology, a Morpholino is a molecule in a particular structural family that is used to modify gene expression. Morpholino oligomers are an antisense technology used to block access of other molecules to specific sequences within nucleic acid...

 antisense.

See also

  • DNA
    DNA
    Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

  • DNA codon table
    DNA codon table
    The genetic code is traditionally represented as a RNA codon table due to the biochemical nature of the protein translation process. However, with the rise of computational biology and genomics, proteins have become increasingly studied at a genomic level. As a result, the practice of representing...

  • Viral replication
  • RNA Virus
    RNA virus
    An RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...

  • Antisense therapy
    Antisense therapy
    Antisense therapy is a form of treatment for genetic disorders or infections.When the genetic sequence of a particular gene is known to be causative of a particular disease, it is possible to synthesize a strand of nuc acid that will bind to the messenger RNA produced by that gene and inactivate...

  • Transcription
    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...

  • 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...

  • Directionality (molecular biology)
    Directionality (molecular biology)
    Directionality, in molecular biology and biochemistry, is the end-to-end chemical orientation of a single strand of nucleic acid. The chemical convention of naming carbon atoms in the nucleotide sugar-ring numerically gives rise to a 5′-end and a 3′-end...

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