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Gene regulation

By Levi Clancy for Student Reader on

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Transcriptional control

Some signals can be small molecules entering cells called effectors. Transcription and translation are collectively called gene expression. Constitutive proteins are needed at all times under all growth conditions. Two major modes of regulation: activity (posttranslational) and amount (at level of transcription or translatioN). Synthesis stopping need time to take effect while protein gets diluted. Feedback inhibition and isoenzymes are noncovalent inhibition. Allosteric enzymes have active sites and allosteric sites. The effector binds reversibly. The conformation changes and the substrate can no longer bind. Isoenzymes are different proteins catalyzing the same reaction but are subject to different regulatory controls. Concerted feedback inhibition.

SynthesisRegulation of TF synthesis (transcription of the TF gene).
ActivityRegulation of transcription factor (TF) activity (activators and repressors). Regulation of TF activity by interaction with small molecules (ligands), and post-translational modifications, especially phosphorylation and dephosphorylation. Regulates Nuclear transport, import and export; DNA binding to cognate DNA site; Interactions with co-activators.
DegradationRegulation of TF degradation.
ElongationBesides transcription initiation, sometimes elongation is activated for some specific genes. For example, transcription of viral HIV TAR from the LTR promoter by the T cell RNA Polymerase II will stop, and only resume after: the HIV Tat protein has bound the TAR RNA; Cyclin T/CDK9 then binds the Tat protein; and the Pol II CTD is then phosphorylated.

Regulating RNA

Genetic regulatory processes act on RNA as well as DNA. The protein output of genes is regulated at every step in the life of an mRNA from the initiation of synthesis to degradation. The three major processing reactions that generate a mature mRNA from the mRNA precursor are capping, splicing and polyadenylation.

  1. RNA splicing, cleavage & polyadenylation.

  2. Degradation of improperly processed RNA.

  3. Cell-type-specific RNA editing.

  4. Nuclear export.

  5. Cytoplasmic export.

  6. Translation initiation.

  7. Decapping and mRNA decay.

Translational Control

Activator ProteinProtein binding to specific DNA sequences, stimulating transcription for positive control.
Allosteric EnzymeEnzyme w/ allosteric site (effector binds) and active site (substrate binds). Effector binding causes conformational change so substrate cannot bind. Activity of enzymes regulated: Covalent modification, protein kinase adds phosphate group to hydroxyl of serine, threonine, or tyrosine residues is most common, phosphorylation of different sites can either activate or deactivate; proteolytic cleavage where synthesized in inactive forms and activate by cleavage by a protease; association with other polypeptides, some enzymes have catltic activity in one polypeptide subunit, removal of regulatory subunit results in continuous rapid catalysis by the atalytic subunit, known as constitutive activity (constitutive connotes continuous or unregulated); allosteric regulation, the modification of active-site activity through interactions of molecules wit other specific sites on the enzyme called allosteric sites.
AttenuationTranscription terminated after initiation but before full-length mRNA produced.
Feedback InhibitionDecrease in activity of 1st enzyme of pathway caused by final pathway product.
Gene ExpressionTranscription and/or translation of genes.
Heat Shock ProteinsProteins produced by sudden temperature upshift to refold partially denatured proteins.
InductionProduction of enzyme only when substrate is present.
KinaseEnzyme that adds phosphoryl.
Negative ControlRepressor protein preventing transcription of genes or genes.
OperonGroup of genes transcribed into single RNA under control of single promoter all involved in same pathway.
Positive ControlWhen an activator protein functions to promote transcription of gene or genes.
Quorum SensingRegulatory system requiring certain density of same-species cells before regulatory events occur.
RepressionEnzyme synthesis prevention.
Repressor ProteinRegulatory protein binding to DNA sequence, blocking transcription, involved in negative control.
2-ComponentThe 2-Component Regulatory System performs signal transduction with 2 proteins: sensor kinase is a membrane-integrated protein which phosphorylates itself and transfers phosphoryl to a response regulator protein. An external signal is transmitted to an intermembrane sensor kinase, which relays the signal by autophosphorylating a histidine residue on it's cytoplasmic surface. Hence, sensor kinases are histidine kinases. The phosphoryl group is then transferred to the response regulator. This is usually a DNA-binding protein regulating transcription. Phosphatase removes the phospohoryl group from response regulator protein at a constant rate, thus resetting the system.
RiboswitchOn mRNA, binds a molecule near 5' end which alters secondary structure and prevents translation.
Stringent ResponseGlobal regulatory control activated by amino acid starvation.