Control of Factor Expression


By gene expression we hateful the transcription of a cistron into mRNA and its subsequent translation into protein. Gene expression is primarily controlled at the level of transcription, largely every bit a outcome of bounden of proteins to specific sites on DNA. In 1965 Francois Jacob, Jacques Monod, and Andre Lwoff shared the Nobel prize in medicine for their work supporting the thought that control of enzyme levels in cells is regulated by transcription of DNA. occurs through regulation of transcription, which tin can be either induced or repressed. These researchers proposed that product of the enzyme is controlled by an "operon," which consists a series of related genes on the chromosome consisting of an operator, a promoter, a regulator gene, and structural genes.

  • The structural genes contain the code for the proteins products that are to be produced. Regulation of protein product is largely achieved by modulating access of RNA polymerase to the structural gene existence transcribed.
  • The promoter cistron doesn't encode anything; it is merely a Deoxyribonucleic acid sequence that is initial binding site for RNA polymerase.
  • The operator cistron is also non-coding; information technology is just a DNA sequence that is the bounden site for the repressor.
  • The regulator gene codes for synthesis of a repressor molecule that binds to the operator and blocks RNA polymerase from transcribing the structural genes.

The operator gene is the sequence of not-transcribable DNA that is the repressor binding site. There is also a regulator gene, which codes for the synthesis of a repressor molecule hat binds to the operator

  • Example of Inducible Transcription: The bacterium Due east. coli has three genes that encode for enzymes that enable it to separate and metabolize lactose (a carbohydrate in milk). The promoter is the site on DNA where RNA polymerase binds in order to initiate transcription. Yet, the enzymes are usually nowadays in very low concentrations, because their transcription is inhibited past a repressor protein produced past a regulator gene (see the top portion of the figure below). The repressor protein binds to the operator site and inhibits transcription. However, if lactose is present in the environment, it tin can demark to the repressor protein and inactivate it, effectively removing the blockade and enabling transcription of the messenger RNA needed for synthesis of these genes (lower portion of the figure beneath).

The repressor is normall bound to the operator, effectively blocking transcription. If lactose binds to the repressor, the repressor is released, and RNA polymerase can then proceed with transcription.

  • Case of Repressible Transcription: East. coli need the amino acid tryptophan, and the DNA in E. coli too has genes for synthesizing information technology. These genes mostly transcribe continuously since the bacterium needs tryptophan. Still, if tryptophan concentrations are loftier, transcription is repressed (turned off) by binding to a repressor protein and activating it as illustrated below.

Binding of tryptophan to the repressor activates the repressor and prevents RNA polymerase from transcribing more mRNA.

Source: http://biowiki.ucdavis.edu/Under_Construction/BioStuff/BIO_101/Reading_and_Lecture_Notes/Control_of_Gene_Expression_in_Prokaryotes

Control of Gene Expression in Eukaryotes

Eukaryotic cells have similar mechanisms for control of gene expression, merely they are more than circuitous. Consider, for case, that prokaryotic cells of a given species are even so, merely nearly eukaryotes are multicellular organisms with many cell types, so control of gene expression is much more complicated. Not surprisingly, cistron expression in eukaryotic cells is controlled by a number of complex processes which are summarized past the post-obit list.

  • Later fertilization, the cells in the developing embryo become increasingly specialized, largely by turning on some genes and turning off many others. Some cells in the pancreas, for example, are specialized to synthesize and secrete digestive enzymes, while other pancreatic cells (β-cells in the islets of Langerhans) are specialized to synthesis and secrete insulin. Each type of jail cell has a item pattern of expressed genes. This differentiation into specialized cells occurs largely as a effect of turning off the expression of most genes in the cell; mature cells may but use three-5% of the genes present in the cell'south nucleus.
  • Gene expression in eukaryotes may also be regulated through by alterations in the packing of Deoxyribonucleic acid, which modulates the access of the cell'due south transcription enzymes (e.g., RNA polymerase) to DNA. The analogy below shows that chromosomes accept a complex structure. The Dna helix is wrapped around special proteins called histones, and this are wrapped into tight helical fibers. These fibers are then looped and folded into increasingly meaty structures, which, when fully coiled and condensed, give the chromosomes their characteristic appearance in metaphase.

Showing how segments of DNA are wrapped around histones

Source: http://www.78stepshealth.us/plasma-membrane/eukaryotic-chromosomes.html

  • Similar to the operons described in a higher place for prokaryotes, eukaryotes likewise employ regulatory proteins to control transcription, only each eukaryotic gene has its own set of controls. In addition, there are many more than regulatory proteins in eukaryotes and the interactions are much more than complex.
  • In eukaryotes transcription takes place within the membrane-bound nucleus, and the initial transcript is modified before information technology is transported from the nucleus to the cytoplasm for translation at the ribosome s. The initial transcript in eukaryotes has coding segments (exons) alternate with non-coding segments (introns). Before the mRNA leaves the nucleus, the introns are removed from the transcript by a process called RNA splicing (meet graphic & video beneath), and extra nucleotides are added to the ends of the transcript; these non-coding "caps" and "tails" protect the mRNA from attack by cellular enzymes and assist in recognition by the ribosomes.

The initial mRNA transcript has introns, i.e., segments of RNA that are then removed. The remaining exons are then spliced together to create the final transcript which has the correct coding sequence.

Source: http://unmug.com/category/biology/organisation-control-of-genome/

  • Variation in the longevity of mRNA provides yet another opportunity for control of factor expression. Prokaryotic mRNA is very short-lived, only eukaryotic transcripts can last hours, or sometimes even weeks (e.g., mRNA for hemoglobin in the red blood cells of birds).
  • The procedure of translation offers additional opportunities for regulation past many proteins. For instance, the translation of hemoglobin mRNA is inhibited unless iron-containing heme is present in the jail cell.
  • In that location are likewise opportunities for "mail service-translational" controls of gene expression in eukaryotes. Some translated polypeptides (proteins) are cut by enzymes into smaller, active final products. as illustrated in the figure below which depicts post-translational processing of the hormone insulin. Insulin is initially translated as a big, inactive precursor; a signal sequence is removed from the head of the forerunner, and a large central portion (the C-concatenation) is cut abroad, leaving ii smaller peptide bondage which are so linked to each other past disulfide bridges.The smaller final form is the active form of insulin.

Post-translational processing of insulin involves folding, cleavage of the bend, and insertion of disulfide cross-links between the two resulting strands.

Source: http://www.nbs.csudh.edu/chemical science/kinesthesia/nsturm/CHE450/19_InsulinGlucagon.htm

  • Gene expression can as well be modified by the breakdown of the proteins that are produced. For instance, some of the enzymes involved in cell metabolism are broken down shortly later on they are produced; this provides a mechanism for rapidly responding to changing metabolic demands.
  • Gene expression can likewise be influenced by signals from other cells. There are many examples in which a signal molecule (e.one thousand., a hormone) from one prison cell binds to a receptor poly peptide on a target cell and initiates a sequence of biochemical changes (a signal transduction pathway) that event in changes within the target jail cell. These changes can include increased or decreased transcription equally illustrated in the effigy below.

Gene expression being influenced by other cells. The signalling cell elaborates a signal molecule that binds to a receptor on a target cell, setting in motion a sequency of events that initiate synthesis of a particular protein.

Source: http://sites.saschina.org/emily01px2016/2014/eleven/23/a-variety-of-intercellular-and-intracellular-point-transmissions-mediate-gene-expression/

  • The RNA Interference system (RNAi) is notwithstanding another mechanism by which cells control gene expression by shutting off translation of mRNA. RNAi can also be used to close down translation of viral proteins when a jail cell is infected by a virus. The RNAi organization as well has the potential to be exploited therapeutically.

RNAi


Some RNA virus volition invade cells and introduce double-stranded RNA which will use the cells machinery to brand new copies of viral RNA and viral proteins. The jail cell's RNA interference system (RNAi) tin prevent the viral RNA from replicating. Kickoff, an enzyme nicknamed "Dicer" chops any double-stranded RNA it finds into pieces that are almost 22 nucleotides long. Next, protein complexes called RISC (RNA-induced Silencing Circuitous) demark to the fragments of double-stranded RNA, winds it, and then releases one of the strands, while retaining the other. The RISC-RNA complex will and so bind to whatsoever other viral RNA with nucleotide sequences matching those on the RNA attached to the circuitous. This binding blocks translation of viral proteins at least partially, if not completely. The RNAi organization could potentially be used to develop treatments for defective genes that cause disease. The treatment would involve making a double-stranded RNA from the diseased gene and introducing it into cells to silence the expression of that gene. For an illustrated explanation of RNAi, come across the short, interactive Flash module at http://www.pbs.org/wgbh/nova/body/rnai-explained.html

The RNA interference system is too explained more than completely in the video below from Nature Video.

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