Gene expression

Gene expression uses a gene's information to produce functional RNA or a protein. Transcription makes RNA from a DNA template; for a protein-coding gene, biological translation then uses messenger RNA to specify an amino acid chain. Many genes instead produce functional RNA, including transfer RNA and ribosomal RNA, without a translated protein product. See Alberts et al., Molecular Biology of the Cell, 4th edition (2002): from DNA to RNA.

Follow the chosen coding strand $5^{\prime }\text{-}\mathrm{ATGGCTTAA}\text{-}{3}^{\prime }$: transcription of its complementary template gives $5^{\prime }\text{-}\mathrm{AUGGCUUAA}\text{-}{3}^{\prime }$ in messenger RNA. In the stated reading frame, its three codons are AUG, GCU and UAA: methionine, alanine and a stop codon. Thus nine nucleotides specify two amino acid residues followed by termination, not three residues. This is an illustrative coding segment embedded in suitable expression and initiation context, not a claim that an isolated nine-nucleotide RNA is sufficient to initiate biological translation.

The distinction between copying and use explains how biological cells can preserve the same DNA yet produce different products. DNA replication duplicates the record; gene expression selects and uses parts of it. Transcription does not use all DNA at once, and gene expression can be controlled at several steps, including transcription, RNA processing and biological translation. See Clark, Douglas and Choi, Biology 2e: regulation of gene expression. The arrows describe template-directed synthesis: the DNA does not physically turn into a protein, and the messenger RNA does not supply the amino acids from which that protein is assembled.

Silencing of much of one X chromosome in a cell lineage. In a heterozygous retina it can create a mosaic of cells expressing different X-linked opsin variants. That mosaic provides potential spectral diversity but does not by itself establish tetrachromacy.

Expression fluctuations caused by shared variation in cellular conditions, such as expression machinery or growth state. Matched reporters tend to co-vary. For mean-normalized reporters whose intrinsic components are conditionally independent, the squared extrinsic noise equals $⟨xy⟩-1$.

Fluctuations due to individual random events in an expression process, conditional on shared cellular conditions. In a matched dual-reporter measurement, independent reporter fluctuations produce scatter perpendicular to the equal-expression diagonal. For mean-normalized reporters $x,y$, the intrinsic squared noise is $⟨(x-y{)}^2⟩/2$ when reporter-specific measurement noise has been accounted for.

For linear RNA removal and protein production driven by independent additive white noises, the stationary RNA variance is $q_R/(2{\gamma }_R)$ and the protein variance is the displayed expression. Steady count birth-and-death intensities $q_R=2{\gamma }_R⟨R⟩$, $q_P=2{\gamma }_P⟨P⟩$ give the protein Fano factor $1+k_P/({\gamma }_R+{\gamma }_P)$. This specializes arbitrary noise strengths; it is not an identity valid for every additive-noise model.

The expected number of proteins produced by one messenger RNA before its removal. With translation rate $r$ and exponential removal rate ${\alpha }_R$, $b=r/{\alpha }_R$. Independent Poisson translation during an exponential lifetime yields a geometric burst count on nonnegative integers, with variance $b(1+b)$. In the short-message-lifetime limit with independent unit protein removal, the protein Fano factor tends to $1+b$.

For independent Poisson process arrivals of geometric translational bursts with mean $b$, arrival rate $\lambda$, and unit protein removal rate $\alpha N$, the stationary mean is $\bar{N}=\lambda b/\alpha$. Starting with zero molecules, the expected value is $m(t)=\bar{N}(1-e^{-\alpha t})$. The variance satisfies $v^{\prime }=\lambda b(1+2b)+\alpha m-2\alpha v$. An integrating factor gives the displayed expression, and its stationary limit is $\bar{N}(1+b)$. Concentration fluctuations require a specified cell volume to convert concentrations into molecule counts.

Regulation through a diffusible product acting at another genetic locus, contrasted with a local cis-regulatory sequence.

Control over when, where and how much a gene is expressed. Evolutionary changes in expression domains can alter developmental identity without requiring movement of a formed organ.

Movement of RNA from the nucleus to the cytoplasm in the relevant eukaryotic pathway. Processing, recognition and quality control can be coupled to export; export is distinct from transcription or subsequent translation.

The spatial distribution and targeting of messenger RNA within a biological cell. concentration enrichment, total fraction recruited, residence time and transport are different observables.

The ratio of RNA concentration inside an assembly to that outside, with accessible volumes and molecule detection specified. A high concentration ratio does not mean a large fraction of all cellular molecules is recruited.

Degradation of RNA molecules. RNA abundance reflects both production and decay, so a steady-state abundance difference alone does not establish a change in stability.

An RNA sequence element enriched in adenine and uracil that can recruit regulatory proteins affecting RNA stability.

The time for half of an RNA population to disappear under specified conditions. For a homogeneous first-order decay process it equals $\ln 2/k_{\mathrm{d}}$; ongoing synthesis and changing biological cell states complicate abundance measurements.

Artificial recruitment of a candidate effector to a chosen RNA through a separate recognition module. It tests activity after recruitment while bypassing native recognition; physiological targeting and necessity require independent evidence.

Control of the rate or pattern of biological translation. ribosome occupancy depends on initiation and passage, so more occupied ribosomes need not mean more completed protein.

An operational measure often estimated from normalized ribosome footprints relative to RNA abundance. It reflects occupancy per transcript and is not automatically a direct rate of completed protein production.

Imaging newly emerging peptide chains at individual RNA molecules. Release and run-off controls help distinguish translation-dependent signals from aggregates or completed proteins.

Inhibition of uptake of an inducing substrate by a preferred-carbon-source regulatory system. Glucose-dependent inhibition of lactose permease reduces formation of allolactose and reinforces lac operon repression.

An Escherichia coli transcription unit encoding lactose-use proteins. Expression integrates LacI-dependent repression, allolactose induction, catabolite activator protein activation and inducer exclusion.

IPTG is a nonmetabolizable lactose analogue used as an inducer of the lac operon. Binding changes LacI's affinity for the lac operator; it supplies a way to change repressor availability without assuming that cytoplasmic transport is instantaneous.

A DNA recognition sequence bound by LacI. Repeated copies are used in fluorescent operator-repressor chromosome labelling.

A regulatory factor that helps repress target gene expression through recruited molecular interactions. The outcome depends on the bound regulator, promoter and cellular context.

A regulatory factor that helps a transcription activator increase target gene expression, often through interactions with chromatin or the RNA polymerase machinery.

Attenuation in bacterial gene regulation regulates downstream transcription through formation of alternative RNA structures during transcription. In the tryptophan example, translation of a leader peptide influences which structure forms; the immediate decision is transcription termination.

An RNA thermometer uses a temperature-dependent RNA structural equilibrium to regulate expression, often by masking or exposing a translation-initiation region. Demonstration requires a relevant temperature range and sequence-dependent structural controls.

A riboswitch is a structured RNA regulatory element whose ligand-binding state changes gene expression through a coupled expression platform. Depending on the system, the immediate output can be translation-initiation accessibility or transcription termination.

A T7 expression system uses bacteriophage T7 RNA polymerase to transcribe an insert from a recognized promoter. Regulating the supply or activity of that polymerase can control expression. High transcript production can still yield insoluble or inactive protein.

An alteration of an RNA sequence after its synthesis. Sequence-specific recognition and catalytic activity can depend on distinct factors.

A bacterial nutrient-stress response involving (p)ppGpp, reallocating expression away from rapid growth and toward survival and restored nutrient supply.

A regulatory response in which eIF2 phosphorylation reduces general initiation while favoring expression of selected stress-responsive genes, including ATF4 in mammals.

Sequence-directed regulation guided by small RNAs, often through Argonaute. Its effects can include transcript destruction, repression of biological translation or recruitment of repressive chromatin, depending on the pathway.

Generation of small regulatory RNAs without Dicer cleavage. Piwi-interacting RNA production and nematode RNA-dependent RNA polymerase-generated secondary RNAs are important examples.

An Argonaute-containing effector complex guided by small RNA. Target binding can produce cleavage, translational repression or RNA destabilization depending on the guide, effector and target.

A short RNA that guides sequence-specific silencing through an Argonaute protein; different pathways use different lengths and targets.

A class of Caenorhabditis elegans secondary small RNAs with a characteristic 5′ guanine and approximately 22-nucleotide length, generated by RNA-dependent RNA polymerases.

A fission-yeast small-RNA-guided chromatin silencing complex including Argonaute and a methyl-mark-binding component.^[ref]

An assembly of RNA polymerase and associated factors at a gene promoter before productive RNA synthesis. Its positioning and opening of template DNA help determine initiation.

A general transcription factor complex containing activities involved in promoter opening and regulation of RNA polymerase II; some components also function in DNA repair.

A DNA translocase component of TFIIH involved in opening RNA polymerase II gene promoters. It is a molecular target of triptolide.^[ref]

A general transcription factor contributing to assembly and positioning of RNA polymerase II in the preinitiation complex.

A general transcription factor complex containing TATA-binding protein and associated subunits, involved in recognition and assembly at many RNA polymerase II core promoters.

The DNA position corresponding to the first incorporated ribonucleotide in a primary transcript. A processed $5^{\prime }$ end need not identify a transcription start site.

Addition of a poly(A) tail to an RNA end. Its effect and regulation depend on the compartment and transcript class.

An experimentally introduced gene whose measurable output reports a specified regulatory process. A change in protein output alone cannot distinguish altered transcription, RNA decay and biological translation.

A sequence element acting on expression or processing of the molecule or locus carrying it. A binding motif in an intron can regulate nearby alternative splicing, with its effect depending on position and the available RNA-binding proteins.

A DNA sequence recognized by an activated hormone-regulated transcription factor. It connects ligand-dependent regulator activity to a particular target gene.

An RNA surveillance pathway that removes certain transcripts after a termination event interpreted in an abnormal context. It can alter observed transcript isoform abundance after RNA splicing, so mature abundance is not always a direct measure of the production ratio.

A member of the UPF surveillance-factor system. Artificial recruitment downstream of a termination codon can trigger nonsense-mediated decay when the required downstream machinery is present.

One of the distinct RNA products associated with a gene, differing through initiation, RNA splicing, end formation or other processing. Different transcript isoforms need not encode different proteins.

gene overexpression produces more of a gene product than the chosen reference state. Increased protein concentration can alter occupancy or create associations absent at endogenous abundance.

Measurement of the relative expression of distinguishable alleles within the same sample. In an informative hybrid, the shared cellular environment helps test local regulatory differences, but mapping bias and parent-of-origin effects can complicate interpretation.

Use of DNA sequencing of RNA-derived material to characterize expressed products and their abundances. Tissue composition and developmental stage must be controlled when comparing gene expression across lineages.

A method for detecting differential RNA-modification signals using Gaussian mixture distributions of nanopore current, with condition-specific component proportions. A shifted signal requires biological interpretation as well as statistical separation.^[ref]

A nuclear run-on and capped-end mapping method for characterizing transcription initiation. It is useful for comparing nascent initiation with the surviving mature transcript population.^[ref]

Cap analysis of gene expression: sequencing capped RNA ends to characterize start-site usage. Differential survival or capping of transcripts can alter the observed distribution without a matching change in nascent initiation.

Thiol-linked alkylation used with metabolic RNA labelling to identify newly synthesized RNA through characteristic sequencing changes after 4-thiouridine incorporation.^[ref]

Profiling RNA from individual isolated cell nucleus preparations. The preparation samples nuclear and often incompletely processed transcripts, so its intron counts are not interchangeable with mature cytoplasmic messenger RNA counts.

Sequencing designed to span long portions of individual RNA molecules or derived Complementary DNA. Linking distant exons on one molecule helps resolve complete transcript isoforms, while per-base errors and sampling depth still require control.

A regulatory DNA region that can increase gene expression in a suitable cellular context through interactions with regulatory machinery. The specificity of an enhancer can permit cis-regulatory evolution of one developmental deployment.

Physical proximity between an enhancer and a promoter measured or inferred in chromatin experiments. A contact does not by itself establish a regulatory effect.

Evolutionary change in DNA sequences that regulate gene expression on the same molecule. A tissue-specific enhancer can change one deployment of a gene while preserving others, although regulatory changes can themselves have pleiotropy.

Dependence of gene expression on an allele's parental origin. Disrupted genomic imprinting can make reciprocal hybrid crosses differ in embryonic growth.^[ref]

An explanation in which maternally and paternally inherited copies differ in relatedness to recipients affected by gene expression, generating different favoured expression levels.

The establishment of substantial embryonic transcription after fertilisation. Minor earlier transcription and later major waves make the onset a process rather than one universally instantaneous event.

In the GAL1 gene promoter system used in the yeast cross-species complementation experiment, the inducing sugar galactose promotes gene expression from the engineered construct, whereas glucose provides a noninducing comparison. The comparison concerns an imposed regulatory system, not the donor species’ native regulation. ^[ref]

A gene promoter is a DNA region involved in initiating transcription. Moving a coding sequence into a nuclear genome does not guarantee that its original gene promoter can drive nuclear gene expression.

A plastid gene promoter directing expression of a photosystem II component. A blue-light-responsive promoter in Arabidopsis thaliana is regulated through SIG5.

The region containing sequence information used for local assembly and initiation by the transcription machinery. Different architectures can support focused or dispersed transcription start sites.

A core promoter element overlapping a transcription start site. In focused human gene promoters, its position has a defined relationship to initiation.^[ref]

A core promoter sequence element recognized by TATA-binding protein. Its position and spacing relative to other elements can affect initiation geometry.

A transcription factor is a protein that regulates transcription. Combinations of transcription factors help select gene expression patterns during cell differentiation. ^[ref]

A Drosophila transcription factor supplied through maternal and zygotic expression. Posterior Nanos-dependent repression of the maternal messenger RNA and anterior Bicoid-dependent transcription make distinct contributions.

A Drosophila maternal homeodomain protein concentrated anteriorly. It activates zygotic transcription in a concentration-dependent context and also represses translation of Caudal messenger RNA.

A forkhead-family transcription factor associated with axial mesendoderm and definitive endoderm specification.

A signal-responsive transcriptional effector that can act with SMAD2 in Nodal-related developmental signalling.

A signal-responsive transcriptional effector of Nodal and related TGF-beta-family pathways.

A TEAD-family transcription factor whose activity with YAP participates in mouse trophectoderm specification.

A Caudal-related transcription factor supplying an additional input into the Caenorhabditis elegans endomesoderm network.

A divergent Caenorhabditis elegans beta-catenin coactivator that binds POP-1. A high SYS-1-to-POP-1 ratio supports transcriptional activation in the appropriate posterior daughter.

The Caenorhabditis elegans TCF-family transcription factor. Its action depends on nuclear abundance and availability of SYS-1, so it can repress or activate endoderm targets in different daughter cells.

A GATA transcription factor acting with ELT-2 across the specification-to-differentiation transition in the Caenorhabditis elegans intestine.

A GATA transcription factor important in intestinal differentiation and maintenance in Caenorhabditis elegans, with overlapping functions with ELT-7.

A transient GATA transcription factor acting in early Caenorhabditis elegans endoderm specification and contributing to END-1 activation.

A GATA transcription factor specifying Caenorhabditis elegans endoderm, with overlapping function with END-3. Forced expression can test bypass of an earlier regulatory requirement.

A divergent GATA transcription factor acting with MED-1. Parallel regulatory inputs mean that loss of the MED factors need not eliminate every intestinal cell in every embryo.

A divergent GATA transcription factor contributing to the robustness of Caenorhabditis elegans endomesoderm specification, partly redundantly with MED-2.

A maternal transcription factor providing endomesodermal input to the EMS lineage in Caenorhabditis elegans. Its effects include activation of MED factors and endoderm-specifying regulators.

A transcription factor family recognizing GATA-related DNA motifs. Successive GATA factors can implement specification, stabilization and differentiated gene expression in a developmental gene regulatory network.

A family of transcription factors connecting phytochrome signaling to growth and development. Family members have distinct targets and regulatory interactions.