Nucleic acid

A nucleic acid is a polymer built from linked nucleotides. The two principal kinds are DNA and RNA. Each nucleotide contributes a sugar, a nucleobase, and phosphate to the chain; the nucleobase is only the letter-bearing component, not the entire nucleotide. DNA uses deoxyribose, whereas RNA uses ribose. A chain of six nucleotides is therefore not six free nucleobases placed beside one another. See NHGRI: nucleic acids.

The chemical scaffold and the variable lettering do different jobs. Covalent bonds maintain the sugar–phosphate backbone, while the order of attached nucleobases specifies the nucleic acid sequence. A phosphodiester bond links the $3^{\prime }$ position of one sugar to the $5^{\prime }$ position of the next through phosphate. These position numbers refer to carbon chemical atoms in the sugar; they define a strand's direction even when it bends or forms a circle. See Brown, Genomes, 2nd edition: the human genome.

This division is useful: the backbone supplies a connected physical record, and base pairing allows its letters to recognize partners. DNA replication copies that record, and transcription uses a DNA template to make RNA. RNA can also fold into functional shapes through base pairing within one chain; a nucleic acid sequence specifies chemical order, not a requirement for a straight shape. The beauty is that the same kind of polymer can carry a message and form a structure that acts on messages.

A DNA-RNA hybrid pairs a DNA strand with an RNA strand. Its backbone constraints commonly favour A-like duplex geometry, which can alter accessibility relative to B-DNA.

A nucleic acid sequence records the ordered nucleobases of a nucleic acid strand, conventionally read from $5^{\prime }$ to $3^{\prime }$. The standard DNA alphabet is adenine A, cytosine C, guanine G, and thymine T; the standard RNA alphabet uses uracil U in place of thymine T. Each letter denotes the nucleobase attached to one nucleotide, so the six-letter DNA nucleic acid sequence $5^{\prime }\text{-}\mathrm{ACGTAC}\text{-}{3}^{\prime }$ describes six linked nucleotides. See NHGRI: representing DNA by a sequence of letters.

Order carries information that composition loses. Both ACGTAC and AACCGT contain two adenine, two cytosine, one guanine, and one thymine nucleobase, but their nucleic acid sequences differ at positions 2, 3, 4, 5, and 6. At position 2, for example, the first has cytosine and the second adenine. Reporting only the four counts cannot reconstruct either ordered record.

To obtain the partner of $5^{\prime }\text{-}\mathrm{ACGTAC}\text{-}{3}^{\prime }$, apply the DNA base pairing rules position by position: A selects T, C selects G, G selects C, T selects A, A selects T, and C selects G. Alignment gives $3^{\prime }\text{-}\mathrm{TGCATG}\text{-}{5}^{\prime }$. Its opposite end labels matter because the two are antiparallel nucleic acid strands. Reading the partner from its own $5^{\prime }$ end reverses the aligned lettering and yields the reverse complement, $5^{\prime }\text{-}\mathrm{GTACGT}\text{-}{3}^{\prime }$.

Reversal alone gives CATGCA; complementation alone gives aligned TGCATG. Neither operation alone gives the partner written in the usual $5^{\prime }$-to-$3^{\prime }$ convention. Applying the reverse complement operation twice returns ACGTAC: GTACGT complements to CATGCA, which reverses to ACGTAC. This convention makes a single reported strand sufficient to specify an ideally complementary DNA duplex, provided its direction is known.

The fraction or percentage of guanine and cytosine residues in a nucleic-acid sequence. Composition contributes to duplex stability but does not establish primer specificity.

A nucleotide sequence obtained by reversing the order and complementing each nucleobase according to the appropriate base pairing rules.

A base pair is an association of two nucleobases through hydrogen bonds in a compatible arrangement. It commonly joins opposite strands of a nucleic acid double helix, but can also join two regions of one folded RNA strand. Canonical Watson–Crick DNA base pairs match adenine with thymine and guanine with cytosine; canonical RNA base pairs use adenine with uracil instead. The nucleobases belong to complete nucleotides, including their attached sugars and backbone phosphate. See NHGRI: base pair.

The abbreviation bp also measures the length of a paired region. Our ACGTAC/TGCATG duplex has six base pairs, containing twelve nucleotides altogether. Its upper strand contains two adenine, two cytosine, one guanine, and one thymine nucleobase; the lower contains one, one, two, and two respectively. Combined, the counts are three of each nucleobase. Equality of total adenine and thymine, or of total guanine and cytosine, need not hold within either individual strand.

Base pairing is the recognition and association of compatible nucleobases. In canonical Watson–Crick geometry, an adenine–thymine base pair has two hydrogen bonds, while a guanine–cytosine base pair has three. These counts refer to those specific geometries and usual chemical forms; they are not a definition of every possible base pair. RNA can also contain other pairings, and canonical adenine–uracil pairing replaces adenine–thymine pairing. See Clark, Douglas and Choi, Biology 2e: DNA structure.

For this illustrative duplex, the six base pairs are A–T, C–G, G–C, T–A, A–T, and C–G. Thus three contribute two hydrogen bonds each and three contribute three each:Each dotted connector in the diagram counts one hydrogen bond; coloured boxes denote whole nucleobases, not individual chemical atoms. The solid rails denote the covalent bond scaffold. Separating the two strands disrupts base pairing and base stacking without requiring the backbone to be cut.

The count of fifteen hydrogen bonds is not fifteen identical contributions to a duplex's Gibbs free energy. Base stacking, interactions with water and ions, temperature, and the order of neighbouring base pairs also matter. Knowing the fraction of guanine–cytosine base pairs alone does not fix a nucleic acid double helix's shape or stability. See Brown, Genomes: pairing and stacking interactions. What makes base pairing especially useful is its selectivity: an exposed DNA strand constrains the partner's nucleic acid sequence, giving DNA replication a chemical recognition rule.

Watson-Crick base pairing is the canonical geometry of pairing between complementary nucleic-acid bases, including adenine–thymine and guanine–cytosine in ordinary DNA. It is a particular pairing geometry, not a synonym for every possible base pair.

nucleic acid complementarity is the relation between sequences that permits specified base pairs to form when aligned with appropriate strand orientation. In homologous recombination, structural organization helps test pairing rather than reading one fixed base sequence.

A nucleic acid double helix consists of two nucleic acid strands winding around a common axis. In the familiar DNA arrangement, sugar–phosphate backbones lie outside and paired nucleobases lie inside, stacked along the axis. The strands are antiparallel nucleic acid strands. The flattened base pairing ladder above displays partners and direction; winding that ladder into a helix adds spatial organization. RNA can also form double-helical paired regions, so the geometry is not exclusive to DNA. See Alberts et al., Molecular Biology of the Cell: DNA structure.

The useful surprise is that a structure explains a copying principle. Complementary base pairs allow each DNA strand to specify the other's nucleic acid sequence; separate strands can each act as templates in DNA replication. This is a structural constraint, while the enzymes and stages of DNA replication supply the actual process. A nucleic acid sequence specifies letter order without, by itself, giving every detail of the three-dimensional helix.

On 25 April 1953, James Watson and Francis Crick published a model with two oppositely directed chains, outside phosphate groups, and specific base pairs. Their short paper explicitly connected this pairing to a possible copying mechanism, while describing the model as requiring further experimental tests. See the original ^[ref], with an accessible ^[ref].

Rosalind Franklin and Raymond Gosling's paper in the same issue had a different role: it presented X-ray diffraction evidence from DNA fibres and its structural interpretation, including the helical character of the wetter B form and evidence for phosphate groups on the outside. They distinguished forms produced at different water contents and assessed compatibility with the Watson–Crick model. Read their original ^[ref]. The model and the experimental analysis are distinct contributions; a diffraction pattern is evidence constraining a molecular geometry, rather than a direct picture of letter-by-letter base pairing.

Two nucleic acid strands with opposite directional alignment: a $5^{\prime }$-to-$3^{\prime }$ direction on one is aligned with the $3^{\prime }$-to-$5^{\prime }$ direction on the other.

Base stacking is the close arrangement and interaction of neighbouring nucleobases with their approximately planar faces above one another. Along a nucleic acid double helix, neighbouring base pairs stack successively; base pairing instead associates partners across the two strands. Both affect duplex stability, and the interactions depend on the identities and arrangement of neighbouring nucleobases. See Brown, Genomes: base pairing and base stacking.

A DNA hairpin is a stem-loop formed within one DNA strand. Complementary arms can pair while intervening bases form a loop; bases outside the paired arms remain overhangs.

Deoxyribonucleic acid, or DNA, is a nucleotide polymer that stores biological information in its nucleotide sequence. The crucial variable is order: two DNA molecules can contain the same numbers of each nucleobase yet carry different nucleotide sequences. This makes a physical molecule an inheritable record, rather than merely a mixture of ingredients. Genes are functional regions of that record; the whole DNA nucleotide sequence is not one long gene. See NHGRI: DNA fact sheet.

Each DNA strand has a backbone of alternating deoxyribose sugars and phosphate groups joined through covalent bonds. Attached nucleobases supply the familiar four-letter alphabet: adenine A, thymine T, guanine G, and cytosine C. In ordinary double-stranded DNA, base pairing matches A with T and G with C. The backbone connects successive nucleotides along a strand; base pairing connects partners across strands. Keeping these two connections distinct explains how strands can separate while each retains its own nucleotide sequence.

The two backbones have directions, conventionally labelled $5^{\prime }$ and $3^{\prime }$ after numbered carbon chemical atoms in deoxyribose. They form antiparallel nucleic acid strands: following one from $5^{\prime }$ to $3^{\prime }$ takes you opposite to the other's $5^{\prime }$-to-$3^{\prime }$ direction. For the chosen DNA nucleotide sequence $5^{\prime }\text{-}\mathrm{ATGCC}\text{-}{3}^{\prime }$, write its partner directly underneath as $3^{\prime }\text{-}\mathrm{TACGG}\text{-}{5}^{\prime }$. Now read that partner from its own $5^{\prime }$ end: its reverse complement is $5^{\prime }\text{-}\mathrm{GGCAT}\text{-}{3}^{\prime }$. Complementing letters and reversing their order are separate operations. See Alberts et al., Molecular Biology of the Cell: the structure and function of DNA.

The diagram's rails represent sugar–phosphate backbones and its coloured blocks represent nucleobases, not individual chemical atoms. Reading left to right gives five matched positions: A–T, T–A, G–C, C–G, C–G. There are two A–T-type base pairs and three G–C-type base pairs; the complete two-strand example contains ten nucleotides. Reversing the bottom row changes the reading convention, not the physical partners. Real double-stranded DNA winds into a nucleic acid double helix; the flattened ladder emphasizes base pairing and direction without pretending to show its three-dimensional geometry.

The motivating consequence is copying by a template. After strands separate, each existing DNA strand specifies which incoming nucleotides should accompany it through base pairing. DNA replication uses enzymes to build complementary strands, allowing the record to persist through successive biological cells. Base pairing supplies a selection rule, while enzymes perform the chemistry: a matching diagram alone is not a complete copying mechanism. The connection between structure and copying was already central to the model published by Watson and Crick on 25 April 1953. See Watson and Crick, Molecular Structure of Nucleic Acids, Nature 171, 737–738 (1953).

Stored information needs interpretation. Some DNA regions specify proteins through RNA; others contribute to functional RNA or regulate gene expression, and some have no known function. Non-coding DNA means sequence that does not specify a protein's sequence of amino acids, not automatically useless sequence. Nor does a DNA nucleotide sequence alone determine an organism's fate: phenotypes also depend on biological context and environment. See NHGRI: non-coding DNA. Its double-stranded form is often modeled mechanically as a worm-like chain, with elasticity and effective excluded volume depending on solvent conditions.

DNA melting is local or extensive separation of the two strands when stabilizing base pairing and stacking no longer maintain a duplex. Temperature, chemical environment or proteins can favour opening; a transcription initiation bubble is a localized example.

An assay asking whether nucleic acid remains inaccessible to a nuclease under specified conditions. Protection can reflect protein binding or compartmental enclosure; appropriate disruption controls distinguish them.

A chemical or structural alteration of DNA that can disrupt its normal function or copying. Damage, activation of a damage response and successful repair are separate measurements.

Physical discontinuity of a chromosome. Fluorescent locus splitting or undercondensation can suggest vulnerability but needs additional evidence before being equated with a break.

DNA recovered from historical or prehistoric biological material. Authentication must distinguish endogenous sequence from contamination and account for short fragments and damage.

DNA looping brings separated sequence positions into spatial proximity through bending and folding of the DNA. In transcriptional regulation it can permit a distant regulatory protein to influence promoter-associated machinery, although proximity alone does not prove productive activation.

Negative supercoiling describes torsionally constrained DNA with linking number below its relaxed reference value. Under appropriate conditions this stress can favour local strand opening or a transition to a different helical conformation, including Z-DNA.

The minor groove of duplex DNA exposes a different set of base edges from the major groove. Similar chemical patterns for some oriented base-pair alternatives limit simple direct readout, but groove shape, hydration and electrostatics can still contribute to specificity.

The major groove of an ordinary B-DNA duplex exposes base-pair edges whose donor, acceptor and hydrophobic patterns distinguish oriented base pairs. Groove accessibility changes with helical conformation, and protein recognition can combine these patterns with backbone and shape contacts.

A DNA double helix contains two antiparallel, base-paired DNA strands wound around a common axis. Handedness and groove geometry can change between conformational families without changing the basic fact of duplex pairing.

Z-DNA is a left-handed duplex family with a zigzag backbone and alternating nucleotide conformations. Alternating purine–pyrimidine sequences can favour it; local torsional stress and binding partners influence its occurrence. Left-handed nucleosome wrapping is a different structural level.

B-DNA is the familiar hydrated right-handed duplex family, with predominantly C2′-endo sugars and accessible major groove base edges. Its local geometry varies with sequence and bound molecules; approximately 10.5 base pairs per turn is an average rather than an exact universal repeat.

A-DNA is a right-handed duplex family with predominantly C3′-endo sugar puckering, tilted and displaced base pairs, and a deep narrow major groove. Double-stranded RNA and many DNA-RNA hybrids have related A-form geometry.

Twisting of the axis of double-stranded DNA associated with torsional constraint. Supercoiling can influence the energetic cost of local strand opening.

heteroduplex DNA is a duplex whose strands originate from different parental molecules. Related but nonidentical sequences can introduce mismatches; heteroduplex formation does not require that every position be mismatched.

double-stranded DNA contains two associated DNA strands, ordinarily paired through base pairing. Their separation and re-pairing underlies DNA strand exchange.

single-stranded DNA is DNA present as one polymer strand rather than an ordinary paired duplex. It can form secondary structures or associate with proteins; single-stranded does not imply an entirely straight, unstructured chain.

A DNA lesion is physical or chemical damage to DNA, such as an altered nucleobase or strand break. DNA repair can restore the sequence before a lasting mutation occurs.

Ribonucleic acid, or RNA, is a nucleotide polymer whose nucleotide sequence can both carry information and organize a working molecular shape. Its backbone contains alternating ribose sugars and phosphate groups connected through covalent bonds. Its usual nucleobases are adenine A, uracil U, guanine G, and cytosine C. Thus RNA uses U where DNA uses T; its ribose also differs chemically from DNA's deoxyribose. See NHGRI: RNA.

In transcription, an enzyme uses one DNA strand as a template for RNA. For example, the DNA template $3^{\prime }\text{-}\mathrm{TACGG}\text{-}{5}^{\prime }$ specifies $5^{\prime }\text{-}\mathrm{AUGCC}\text{-}{3}^{\prime }$ in RNA. The base pairing rules now include A–U rather than A–T, while G–C remains. This RNA matches the other DNA strand's $5^{\prime }$-to-$3^{\prime }$ lettering after T is replaced by U. Identifying the template strand matters: replacing T by U in an arbitrarily chosen DNA strand is not a general method for deriving the RNA product. See Alberts et al., Molecular Biology of the Cell: from DNA to RNA.

RNA is often a single strand, but single-stranded does not mean straight or entirely unpaired. Complementary regions within one RNA molecule can undergo base pairing, bringing distant positions together. Consider the illustrative twelve-nucleotide nucleotide sequence $5^{\prime }\text{-}\mathrm{GCAUUUUUAUGC}\text{-}{3}^{\prime }$. Pair positions 1 with 12, 2 with 11, 3 with 10, and 4 with 9. The resulting stem-loop has four base pairs: G–C, C–G, A–U, U–A. Positions 5–8 remain unpaired in the loop. Both arms belong to the same continuous backbone, and the paired arms have the directions of antiparallel nucleic acid strands.

The diagram proposes a possible pairing pattern, not a prediction that this short RNA must adopt that shape under every condition. Actual RNA folding depends on additional interactions, temperature, ions, and associated proteins; the full three-dimensional arrangement contains more information than the drawn base pairs. The example's purpose is to show how a linear nucleotide sequence can specify contacts within itself.

Different RNA roles make this flexibility useful. Messenger RNA carries a message that a ribosome reads during translation to build a protein. Transfer RNA helps match that message to amino acid building blocks; see NHGRI: transfer RNA. Ribosomal RNA forms structural and catalytic parts of the ribosome. Other RNA participates in gene regulatory networks, changing how strongly genes are expressed. Many RNA molecules therefore function without being translated into proteins; for some genes, functional RNA is the product itself.

Most strikingly, some folded RNA acts as an enzyme: these catalytic RNA molecules are ribozymes. The ribosome's bond-forming active site is built from RNA, although the complete ribosome also contains proteins. Structural evidence appears in Nissen et al., The structural basis of ribosome activity in peptide bond synthesis, Science 289, 920–930 (2000). RNA therefore connects a readable record with physical recognition, regulation, and catalysis: the same kind of polymer can be a message, an adaptor, or part of molecular machinery.

The hypothesis proposes an early hereditary system in which RNA or closely related molecules carried sequence information and performed important catalytic functions. Modern ribozymes, self-splicing introns and the RNA-centred ribosome demonstrate relevant capacities; they do not by themselves prove a complete origin-of-life pathway. Nucleotide availability, copying fidelity, strand separation, energy supply and chemical stability remain separate constraints.

Copying an RNA sequence into RNA using complementary base pairing. It is distinct from transcription of a DNA template and from reverse transcription into DNA.

An RNA whose folded structure binds a target with molecular specificity. Binding affinity can be expressed by a dissociation constant; it does not by itself fix binding and unbinding rates. Recognition can be coupled conceptually to an optical readout without altering the target's genetic material.

An RNA duplex formed by complementary strands or self-complementary segments. Purified duplex and single-strand controls distinguish a double-stranded trigger from a simple antisense effect in RNA interference.

A class of small noncoding RNA involved in nucleolar RNA processing and modification pathways. Some are generated from intronic sequences.

The spatial distribution and directed or selective positioning of RNA within a cell or tissue.

An RNA pseudoknot forms when nucleotides in a loop pair with a region outside that loop, producing an interleaved pairing topology. Some pseudoknots resist ribosomal unwinding and contribute to programmed recoding.

A small regulatory RNA can alter target-RNA translation or stability through base pairing or protein interactions. In bacteria, effects on initiation and RNA degradation should be separated experimentally with transcript and protein measurements.

A guide RNA associated with Piwi-family proteins. Most characterized animal piRNA pathways use Dicer-independent processing of single-stranded precursors; the approximately 21-nucleotide C. elegans 21U RNAs are distinct from the longer typical fly and mammalian piRNAs.^[ref]

A class of approximately 21-nucleotide Caenorhabditis elegans piRNAs associated with PRG-1. They are not generated by the standard fly ping-pong system.

Reciprocal guide-directed cleavage produces new piRNA ends from complementary precursor or target RNAs. A 10-nucleotide overlap of opposite-strand 5′ ends supports this mechanism but does not prove amplification in every piRNA pathway.

A genomic source of piRNA precursor transcripts, often containing fragments of transposable elements. Cluster-derived guides can recognize related active elements elsewhere in the genome.

A small regulatory RNA that guides an Argonaute-containing complex to target RNAs, influencing their stability or biological translation.

A Caenorhabditis elegans microRNA regulating developmental timing through targets including lin-14. It demonstrates developmental use of a small RNA rather than only defence against foreign sequences.

Recruitment of RNA decay machinery by a microRNA-bound effector can shorten the target poly(A) tail and reduce stability, often together with translational repression.

A mobile plant microRNA that can move from shoot to root and repress TML. Its abundance helps regulate susceptibility to rhizobial infection in Lotus japonicus.

A target altered so that a tested microRNA can no longer regulate it while preserving the relevant target function. Rescue tests should control expression level and native RNA context.

An introduced RNA designed to reproduce a mature microRNA guide activity. Delivery, dosage, unintended interactions and immune activation constrain inference from microRNA mimic experiments.

A liposomal miR-34a microRNA mimic studied in a phase 1 trial. Serious immune-related toxicity illustrates limits of inferring therapeutic safety from endogenous regulatory function.^[ref]

A short guide-RNA segment important for recognition of many targets. Seed matching supports target prediction but does not establish functional regulation by itself.

A microRNA family with members inducible by p53 in appropriate contexts. Forced expression and endogenous requirement are distinct: complete family deletion did not abolish the tested p53 responses in one mouse study.^[ref]

A microRNA locus associated with the miR-15a cluster. Locus-specific genetic tests should be distinguished from perturbation of other related family members.

A microRNA encoded with miR-16-1 in a cluster implicated in B-cell proliferative control. The broader deleted genomic region can have effects beyond the miRNA genes.

A conserved microRNA family involved in developmental regulation and repression of growth-related targets, with demonstrated tumour-suppressive activity in selected models.

The pattern of local and long-range base pairing within RNA. Pairing can hide a binding motif or an initiation region, making accessibility an experimentally testable regulatory variable.

Bringing separated RNA segments into proximity while an intervening segment forms a loop. Multivalent RNA-binding proteins can stabilize this geometry, with consequences for accessibility and splice-site use.

A structured RNA recognition element bound by iron regulatory proteins. In suitable 5′ contexts it controls biological translation, whereas a 3′ stability-control context can regulate RNA decay. It is not an autonomous iron-sensing riboswitch.

A regulatory mechanism in which a chemical modification changes RNA secondary structure and thereby exposes or occludes a functional element. Modification dependence of binding alone does not distinguish this mechanism from direct chemical recognition.^[ref]

A Drosophila transcript whose anterior translation is repressed by Bicoid, helping establish a posterior Caudal protein distribution despite broad maternal transcript availability.

A Drosophila transcript with distinct maternal and zygotic contributions. Nanos-dependent regulation of the maternal RNA involves response elements in its 3′ untranslated region and shapes the posterior Hunchback protein distribution.

A maternally supplied Drosophila transcript localized at the anterior of the oocyte and early embryo, providing a spatial source of Bicoid protein.

The messenger-RNA region upstream of the principal coding start, which can contain structures and upstream reading frames affecting initiation.

A polycistronic messenger RNA contains multiple protein-coding regions. Their translation can be regulated independently or coupled through local RNA structure and ribosome movement.

The chloroplast transcript encoding D1 protein. Changes in its ribosome recruitment can help couple synthesis to demand for replacement D1 protein.

A transcript encoding a form of actin, with a localization element recognized by ZBP1.

A localized Drosophila melanogaster transcript with an experimentally studied diffusion-and-entrapment mechanism.^[ref]

The segment of a messenger RNA downstream of its translated coding region. It can contain cis-regulatory elements affecting localization, stability and biological translation.

A cis-regulatory messenger RNA element mediating Nanos-dependent regulation through associated RNA-binding proteins. mutation and reporter transfer can test necessity and sufficiency.

Removal of an RNA cap. It can expose an end to degradation and can also change recovery in an assay that selects capped RNAs.

A stretch of adenosine-containing residues at an RNA end. Tail length and associated proteins can influence messenger RNA stability and biological translation.

Shortening of an RNA poly(A) tail. For many cytoplasmic messenger RNAs, this contributes to progression toward decay.

A protein complex with functions in RNA regulation, including deadenylation; its recruitment can connect recognition by a silencing effector to RNA-tail shortening.

The maternal transcript whose local translation produces Oskar; its localisation controls where it can organise germ plasm in Drosophila melanogaster.

The three-nucleotide region of a transfer RNA that recognizes a corresponding codon through base pairing during biological translation.

A transfer RNA carrying an amino acid through an activated ester linkage. Aminoacyl-tRNA synthetase supplies the charging reaction; the linkage helps drive peptide-bond formation.

A transfer RNA charged with methionine. The initiator species has a distinct role in start-site decoding during biological translation.

Polyuridylic acid is an RNA polymer whose nucleotides all carry uracil.