Nucleus Protein synthesis

I Replication—the process by which identical copies of DNA are made so that information can be preserved and handed down to offspring I Transcription-—the process by which the genetic messages are read and carried out of the cell nucleus to ribosomes, where protein synthesis occurs... 

Whereas DNA has a single role as the storehouse of genetic information, RNA plays many roles in the operation of a cell. There are several different types of RNA, each having its own function. The principal job of RNA is to provide the information needed to synthesize proteins. Protein synthesis requires several steps, each assisted by RNA. One type of RNA copies the genetic information from DNA and carries this blueprint out of the nucleus and into the cytoplasm, where construction of the protein takes place. The protein is assembled on the surface of a ribosome, a cell component that contains a second type of RNA. The protein is consfructed by sequential addition of amino acids in the order specified by the DNA. The individual amino acids are carried to the growing protein chain by yet a third type of RNA. The details of protein synthesis are well understood, but the process is much too complex to be described in an introductoiy course in chemistry. 

The eytoplasm is a viscous fluid and contains within it systems of paramount importance. These are the nucleus, responsible for the genehc make-up of the cell, and the ribosomes, whieh are the site of protein synthesis, hi addihon are found granules of reserve material suehas polylydioxybutyric add, an energy reserve, and polyphosphate or volutin granules, the exact funchon of which has not yet been elucidated. The prokaiyohc nueleus or bacterial chromosome exists in the cytoplasm in the form of a loop and is not surrounded by a nuclear membrane. Bacteria cany other chromosomal elements episomes, which are portions of the main chromosome that have become isolated firm it, and plasmids, whieh may be called miniature chromosomes. These are small annular pieees of DNA whieh carry a limited amount of genetic information. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

The testes and adrenal glands produce 90% and 10%, respectively, of circulating testosterone. Testosterone enters prostate cells, where predominantly type II 5a-reductase activates testosterone to dihydrotestosterone, which combines with a cytoplasmic receptor. The complex enters the nucleus and induces changes in protein synthesis which promote glandular tissue growth of the prostate. Thus, 5a-reductase inhibitors (e.g., finasteride and dutas-teride) directly interfere with one of the major etiologic factors of BPH. 

Not all the cellular DNA is in the nucleus some is found in the mitochondria. In addition, mitochondria contain RNA as well as several enzymes used for protein synthesis. Interestingly, mitochond-rial RNA and DNA bear a closer resemblance to the nucleic acid of bacterial cells than they do to animal cells. For example, the rather small DNA molecule of the mitochondrion is circular and does not form nucleosomes. Its information is contained in approximately 16,500 nucleotides that func-tion in the synthesis of two ribosomal and 22 transfer RNAs (tRNAs). In addition, mitochondrial DNA codes for the synthesis of 13 proteins, all components of the respiratory chain and the oxidative phosphorylation system. Still, mitochondrial DNA does not contain sufficient information for the synthesis of all mitochondrial proteins most are coded by nuclear genes. Most mitochondrial proteins are synthesized in the cytosol from nuclear-derived messenger RNAs (mRNAs) and then transported into the mito-chondria, where they contribute to both the structural and the functional elements of this organelle. Because mitochondria are inherited cytoplasmically, an individual does not necessarily receive mitochondrial nucleic acid equally from each parent. In fact, mito-chondria are inherited maternally. 

The protein synthesis machinery reads the RNA template starting from the 5 end (the end made first) and makes proteins beginning with the amino terminus. These directionalities are set up so that in prokaryotes, protein synthesis can begin even before the RNA synthesis is complete. Simultaneous transcription-translation can t happen in eukaryotic cells because the nuclear membrane separates the ribosome from the nucleus. 

Other receptors are soluble proteins that exist in the cell cytoplasm. When complexed with their signaling molecules or ligands, they migrate to the nucleus where the receptor ligand complex binds specifically to sites on the nuclear DNA and controls protein synthesis. 

When the creation of long-term memories— repeated stimulations interrupted by rest periods—was simulated in this preparation by repeated pulses of serotonin, anatomical changes occurred. Specifically, new synaptic connections were created. It is likely that there are two underlying components to formation of new synaptic connections. One is local protein synthesis in the nerve terminal and the other is CREB (cAMP response element binding) dependent transcription in the neuronal nucleus. Of course, serotoiun pulses also stimulated the release of glutamate. So now the question is how repeated pulses of serotonin are related to protein synthesis and formation of new synapses. 

Protein synthesis-regulating receptors (D) for steroids, thyroid hormone, and retinoic acid are found in the cytosol and in the cell nucleus, respectively. 

The nucleotide components required for transcription and replication have to be imported into the nucleus from the cytoplasm, incorporation of these components into RNA leads to primary products, which are then altered by cleavage, excision of introns, and the addition of extra nucleotides (RNA maturation see p. 242). it is only once these process have been completed that the RNA molecules formed in the nucleus can be exported into the cytoplasm for protein synthesis (translation see p. 250). 

Transcription. For expression of a gene—i. e., synthesis of the coded protein—the DNA sequence information has to be converted into a protein sequence. As DNA itself is not involved in protein synthesis, the information is transferred from the nucleus to the site of synthesis in the cytoplasm. To achieve this, the template strand in the relevant part of the gene is transcribed into an RNA (hnRNA). The sequence of this RNA is thus complementary to that of the template strand (3), but— with the exception of the exchange of thy-... 

Before the hnRNA produced by RNA polymerase II (see p. 242) can leave the nucleus in order to serve as a template for protein synthesis in the cytoplasm, it has to undergo several modifications first. Even during transcription, the two ends of the transcript have additional nucleotides added (A). The sections that correspond to the intervening gene sequences in the DNA (introns) are then cut out (splicing see B). Other transcripts—e.g., the 45 S precursor of rRNA formed by polymerase I (see p. 242)—are broken down into smaller fragments by nucleases before export into the cytoplasm. 

Removal of introns from hnRNA to leave only the exons or gene regions involved in directing protein synthesis in the finished mRNA is accomplished within the nucleus by processing on spliceosomes (Figure 11-4). 

Davis FI, Squire LR (1984) Protein synthesis and memory a review. Psychol Bull 96 518-559 Deisseroth K, Heist EK, Tsien RW (1998) Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature 392 198-202 Dinerman J, Dawson TM, Schell MJ, Snowman A, Synder SH (1994) Endothelial nitric oxide synthase localized to hippocampal pyramidal cells implications for synaptic plasticity. Proc Natl Acad Sci U S A 91 4214-4218... 

Budding and release of progeny virus. B. Replicative cycle of an influenza virus, an example of an RNA virus. 1. Attachment. 2. Endocytosis. 3. Influx of H+ through M2 protein. 4. Fusion of the viral envelope with the endosomes membrane, dissociation of the RNP complex, and entry of viral RNA into the nucleus. 5. Synthesis of viral mRNA by viral RNA polymerase. 6. Translation of viral mRNA by host cell s ribosomes. 7. Replication of viral RNA, using viral RNA polymerase, via cRNA replicative form. 8. Assembly of virus particles, and 9. Budding and release of progeny virus. 

FIGURE 6.1 The different stages of protein synthesis. Transcription and processing of RNA messages occur within the nucleus. The mRNA is then transported into the cytoplasm for translation and post-translational modifications. 

The final principal component of the cell is the nucleus. This is located in the center of the cell and is surrounded by a double membrane, the outer layer being derived from the ER of the cytoplasm and the inner layer coming from the nucleus itself. The two leaflets of the double membrane are fused in places, producing nuclear pores that enable the transfer of macromolecules from the cytoplasm to the nucleus. Two important components of the nucleus are chromatin and the nucleolus. Chromatin represents polymers of DNA complexed with protein. The nucleolus is a complex substructure, composed of ribonucleoprotein granules, that controls the synthesis of RNA destined to form the ribosomes of the cytoplasm. Cells engaged heavily in protein synthesis have... 

The hereditary information, or genetic code, resides in the order of the nucleotides in DNA. This information is copied from the DNA in the cell nucleus into molecules of a special RNA, which passes out of the nucleus to the sites of protein synthesis. Here, the code copied into the RNA determines which proteins are synthesized. These, in turn, determine the structure and functions of the cells and of the organism as a whole. 

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