عدد الرسائل : 2879
العمر : 30
الموقع : فى احضان امى مصر
المزاج : الحمد لله على كل حال
جنسيتك : مصر
السٌّمعَة : 12
تاريخ التسجيل : 27/06/2010
|موضوع: Regulation of Gene Expression الثلاثاء فبراير 08, 2011 6:58 pm|| |
Regulation of gene expression(or gene regulation) includes the processes that cells and viruses use to regulate the way that the information in genes is turned into gene products. Although a functional gene product may be RNA or a protein, the majority of known mechanisms regulate protein coding genes. Any step of the gene's expression may be modulated, from DNA-RNA transcription to the post-translational modification of a protein.
Gene regulation is essential for viruses, prokaryotes and eukaryotes as it increases the versatility and adaptability of an organism by allowing the cell to express protein when needed. The first discovered example of a gene regulation system was the lac operon, discovered by Jacques Monod, in which protein involved in lactose metabolism are expressed by E. coli only in the presence of lactose and absence of glucose.
Furthermore, gene regulation drives the processes of cellular differentiation and morphogenesis, leading to the creation of different cell types in multicellular organisms where the different types of cells may possess different gene expression profiles though they all possess the same genome sequence.
Regulated stages of gene expression
Any step of gene expression may be modulated, from the DNA-RNA transcription step to post-translational modification of a protein. The following is a list of stages where gene expression is regulated; the most extensively utilized point is Transcription Initiation:
• Chromatin domains
• Post-transcriptional modification
• RNA transport
• mRNA degradation
Regulation of transcription
Regulation of transcription controls when transcription occurs and how much RNA is created. Transcription of a gene by RNA polymerase can be regulated by at least five mechanisms:
• Specificity factors alter the specificity of RNA polymerase for a given promoter or set of promoters, making it more or less likely to bind to them (i.e. sigma factors used in prokaryotic transcription).
• Repressors bind to non-coding sequences on the DNA strand that are close to or overlapping the promoter region, impeding RNA polymerase's progress along the strand, thus impeding the expression of the gene.
• General transcription factors These transcription factors position RNA polymerase at the start of a protein-coding sequence and then release the polymerase to transcribe the mRNA.
• Activators enhance the interaction between RNA polymerase and a particular promoter, encouraging the expression of the gene. Activators do this by increasing the attraction of RNA polymerase for the promoter, through interactions with subunits of the RNA polymerase or indirectly by changing the structure of the DNA.
• Enhancers are sites on the DNA helix that are bound to by activators in order to loop the DNA bringing a specific promoter to the initiation complex. Enhancers are much more common in eukaryote than prokaryotes, where only a few examples exist.
After the DNA is transcribed and mRNA is formed there must be some sort of regulation on how much the mRNA is translated into proteins. Cells do this by modulating the capping, splicing, addition of a Poly(A) Tail, the sequence-specific nuclear export rates and in several contexts sequestration of the RNA transcript. These processes occur in eukaryotes but not in prokaryotes. This modulation is a result of a protein or transcript which in turn is regulated and may have an affinity for certain sequences.
• Capping changes the five prime end of the mRNA to a three prime end by 5'-5' linkage, which protects the mRNA from 5' exonuclease, which degrades foreign RNA. The cap also helps in ribosomal binding.
• Splicing removes the introns, noncoding regions that are transcribed into RNA, in order to make the mRNA able to create proteins. Cells do this by spliceosomes binding on either side of an intron, looping the intron into a circle and then cleaving it off. The two ends of the exons are then joined together.
• Addition of poly(A) tail otherwise known as poly-adenylation. Junk RNA is added to the 3' end, and acts as a buffer to the 3' exonuclease in order to increase the half life of mRNA.
Regulation of translation
The translation of mRNA can also be controlled by a number of mechanisms, mostly at the level of initiation. Recruitment of the small ribosomal subunit can indeed be modulated by mRNA secondary structure, antisense RNA binding or protein binding. In both prokaryotes and eukaryotes a large number of RNA binding proteins exist, which often are directed to their target sequence by the secondary structure of the transcript, which may change depending on certain conditions, such as temperature or presence of a ligand (aptamer), some transcripts act as ribozymes and self-regulate their expression.
Gene Regulation can be summarized as how they respond:
• Inducible systems (Positive)- An inducible system is off unless there is the presence of some molecule (called an inducer) that allows for gene expression. The molecule is said to "induce expression". The manner in which this happens is dependent on the control mechanisms as well as differences between prokaryotic and eukaryotic cells.
• Repressible systems (Negative)- A repressible system is on except in the presence of some molecule (called a corepressor) that suppresses gene expression. The molecule is said to "repress expression". The manner in which this happens is dependent on the control mechanisms as well as differences between prokaryotic and eukaryotic cells.
Constitutive (Regulatory) genes: genes that are always active, genes that are always "turned on" genes are always needed . The expression of these genes is not regulated. The product of these genes is produced at constant low rates.
Inducible (Structural) genes: These are negatively regulated by specific proteins termed repressors, They are only activated and produce significant amount of proteins when a specific inducing substance (inducer or derepressor) is present. This inducer produces inactivation of the repressor. These genes occupy the same cistron or operon that produce polycistronic mRNA.
Operon, is a linear array of the genes that are involved in a metabolic pathway
Cistron, is the smallest unit of genetic expression that codes for the structure of protein or protein subunit
The functional operon consists of two types of genes:
• Regulatory gene which codes for mRNA responsible for synthesis of specific regulatory protein termed repressor.
• Structural gene which codes for the product of operon (mRNA responsible for synthesis of specific protein or proteins).
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