NUCLEUS: WHERE GENETIC INFORMATION IS STORED
Posted by Surgery on Jul 8, 2008
Genetic information, stored in the form of genes, resides within the nucleus. This information contains the blueprint of the cell. Genes encode for the proteins necessary for cellular function, including metabolic activity, interaction with the environment, cell division, and response to harmful conditions. In addition, genomic material contains segments that give rise to different RNA molecules, which are necessary for the biosynthesis of cellular macromolecules ( Cozaar ). RNA is an important component of the ribosomes, which are particles responsible for protein synthesis. The material inside the nucleus is separated from the cytosol, or the rest of the cell, by a membrane called the nuclear envelope. This membrane contains pores that allow the exchange of substances between nucleus and cytosol. The passage of material through these pores is actively monitored, contributing to the regulation of nuclear activity. The number of genes in the human genome is small; approximately 30,000 genes are distributed among several chromosomes. The size of individual genes, which is usually referred to in base pairs (bps), is variable as is the density of genes within a chromosome. The encoding region on the gene (exons) is usually disrupted by DNA sequences (introns), which do not form part of the final transcriptional product, the messenger RNA (mRNA Cozaar).
Transcription is composed of three steps: initiation, elongation, and termination. Each step is regulated by a particular set of factors. During elongation, RNA polymerase does not proceed at a constant rate, but rather in bursts between pauses. Reversible pausing is the rate-limiting step of transcription, and it depends on the gene being transcribed. During pausing, RNA polymerase can move forward to add more nucleotides to the nascent transcript, or move in reverse excluding the nascent transcript from the site of transcription, which can be removed by a ribonuclease activity present at the active site of the polymerase. This process is important to correct possible errors that occur during transcription. Transcription of genes is carried out by RNA polymerase II. Ribosomal RNA (rRNA Cozaar) is synthesized by RNA polymerase I, while transfer RNA (tRNA), SSrRNA, and 7S RNA (part of the signal recognition particle) are synthesized by RNA polymerase III. The first product of gene transcription, heterogeneous nuclear RNA (hnRNA Cozaar), contains both exons and introns; the latter are removed by a process known as splicing. This process occurs within the nucleus by a large RNA-protein complex named spliceosome. For some genes, splicing results in the production of several mRNAs, which encode related, but different, polypeptides (alternative splicing). Therefore, a single gene could encode different polypeptides with different specificities. The configuration of alternative splicing for a particular gene could be identical or different between various cell types. Thus, alternative splicing could contribute to the divergent pattern of gene expression observed in different tissues. About 50% of the total rate of transcription is due to synthesis of mRNA precursors by RNA polymerase II, which could be blocked by the addition of α-amantin, a fungal toxin. Total transcriptional activity could be inhibited by administration of actinomycin D. Although mRNA precursors comprise half of the normal transcriptional rate, the cellular abundance of RNAs is different. Thus, the composition of total cellular RNA is divided into rRNA (approx. 75%); tRNA, small RNA, which is involved in splicing, and 5S rRNA (approx. 15%); and hnRNA and mRNA (less than 10% Cozaar ) . The discrepancy between transcription rate and abundance of different RNAs is due to their particular stability within the cell. There are about 500,000 copies of different mRNAs per cell at any particular time. These mRNAs correspond to approximately 20,000 different genes, which are simultaneously expressed within a cell at any given state. The majority of these mRNAs are constantly engaged in translation. Pre-mRNA is further processed by a chemical modification at the 5′ end of the transcript, resulting in the addition of a 7-methyl guanosine group, which is known as capping. This modification occurs cotranscriptionally, and it is important in mRNA transport, stability, and translation. Furthermore, a stretch of 50 to 300 adenosine nucleotides is added to the 3′ end of the transcript, which is known as the poly A tail. The poly A tail also plays a role in mRNA transport, stability, and translation. The same mRNA could present poly A tails of different sizes within the same cell. This difference in poly A length seems to be an indicator of the mRNA age. Thus, older mRNA has apparently shorter poly A tails than newly transcribed ones. The presence of the poly A tail within mRNAs has been exploited to isolate mRNA pools from the total cellular RNA population by affinity chromatography on immobilized oligo dT. Moreover, oligo dT is commonly used in the synthesis of complementary DNA (cDNACozaar ). Thus, it is important to differentiate an mRNA from an RNA precursor or transcript. An mRNA is the fully processed transcript, including capping and the poly A tail. When the mRNA is fully processed, it is transported to the cytosol with the help of several proteins via pores on the nuclear envelope.
There are several discrete regions in a mature mRNA. The open reading frame is the region that gives rise to the polypeptide. This area is flanked by untranslated regions (UTRs), which play an important role in message stability and translation. The region upstream from the transcriptional initiation site is involved in gene transcriptional regulation. This region is known as the promoter and contains regulatory elements (groups of nucleic acids), which are binding sites for transcriptional factors and enhancers that participate in the selective transcription of the gene. There is a common sequence very close to the transcription initiation site, the TATA box (TATAAAA Cozaar ), which is recognized by RNA polymerase II, the enzyme responsible for gene transcription. Finally, genes within a chromosome are separated by large stretches of DNA. Because no function has been associated with these regions, scientists have called them junk DNA
The transcription of a particular gene is regulated by cellular proteins that activate and/or modulate the rate of RNA synthesis. These proteins are known as transcriptional factors, and they recognize specific sequences within the promoter region. There are basic transcriptional factors that cooperate with RNA polymerase II to transcribe a gene. Some of these factors contain activities necessary to unwind (helicase Cozaar) a short stretch of the DNA to gain access for the transcriptional system. The second set of transcriptional factors gives specificity to the process of RNA synthesis, such as tissue specificity. Other factors are responsible for activating the transcription of genes necessary for the cellular response to an external stimulus. For example, heat shock factor 1 is activated to drive the expression of heat shock genes in conditions of physiological stress. These genes encode proteins that are necessary to preserve cell function during harmful conditions. Many transcriptional factors are activated by phosphorylation, which results in a conformational change of the protein. More recently, acetylglucosamine moieties, which are attached to serine, threonine, or tyrosine via the hydroxylgroup of these amino acids (O-linked to Cozaar ), have been found to activate transcriptional factors. In other circumstances, transcriptional factors are associated with an inhibitory protein arresting their potential transcriptional activity. This is the case of NF-κB, which drives the expression of many genes, particularly those involved in the inflammatory process. NF-κB is normally present in the cytosol associated with Iκ-Bα, which is an inhibitory protein. When the cell is activated by an external stimulus, such as an inflammatory mediator, Iκ-Bα is phosphorylated and dissociates from NF-κB. Then, NF-κB is free to translocate into the nucleus and activate transcription. To maintain the activated stage of the cell, Iκ-Bα is degraded by the proteosome system. Consequently, the attenuation of NF- activation can only be accomplished by new synthesis of . Transcription of the gene encoding for is stimulated by NF-. Thus, this system has a built-in mechanism to regulate its own expression, like many other cellular systems.
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