| The major products of transcription are the rRNAs, tRNAs, and the mRNAs. These RNAs perform specific functions in the cell. rRNAs interact to form ribosomes, the basic cellular machinery on which protein synthesis occurs. tRNAs function as adapter molecules that translate the information stored in the mRNA nucleotide sequence to the amino acid sequence of proteins. mRNAs carry the genetic information from DNA and direct the synthesis of all proteins in the cell. In eukaryotic cells, each of these classes of RNAs is produced by a specific RNA polymerase (RNA polymerase I, II, or III), while in bacterial cells a single RNA polymerase synthesizes all three classes. The basic structures of rRNAS and tRNAs in eukaryotic and bacterial cells are similar. However, mRNAs from eukaryotic cells have a 5' (m7Gppp) cap and a 3' ([A]n) tail. Prokaryotic cells do not have these modifications on their 5' and 3' ends and can be polycistronic. In addition, most eukaryotic mRNAs must undergo a process called splicing to be functional, whereas prokaryotic mRNAs are functional as soon as they are synthesized. Splicing involves the removal of sequences called introns and the joining of other sequences called exons to each other to form a functional mRNA. The process of transcription consists of three parts; initiation, elongation, and termination. Initiation involves the recognition by RNA polymerase of the specific region of DNA that is to be transcribed. To accomplish this, RNA polymerases interact with specific DNA sequences called promoters located upstream (before 5' end) to the start of transcription. Elongation involves the selection of the appropriate nucleotide, as determined by the DNA strand, and formation of the phosphodiester bridges that exist between each nucleotide in an RNA molecule. Finally, termination involves the dissociation of the RNA polymerase from the DNA template. This can be accomplished by either RNA secondary structure or specific protein factors.
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- Which commonly used antibiotics are directed at inhibition of bacterial RNA polymerase but do not affect the mammalian complex? Why are these drugs less effective against fungal infections?
- Review the pathogenesis of systemic lupus erythematosus, an autoimmune disease in which antibodies to ribonucleoprotein particles are implicated in the development of chronic inflammation.
- Review the pathogenesis of the thalassemias, with emphasis on those variants in which gene mutations affect the synthesis, processing and splicing of the RNA for hemoglobin, leading to anemia.
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| Akusjarvi G, Stevenin J. Remodeling of the host cell RNA splicing machinery during an adenovirus infection. Curr Top Microbiol Immunol 2003;272:253-286.
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| Herman T, Westhof E. RNA as a drug target: chemical, modeling, and evolutionary tools. Curr Opin Biotechnol 1998;9:66-73.
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Jarad G, Simske JS, Sedor JR, Schelling JR. Nucleic acid-based techniques for post-transcriptional regulation of molecular targets. Curr Opin Nephrol Hypertens 2003;12:415-421.
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| Khan AU, Lal SK. Ribozymes: a modern tool in medicine. J Biomed Sci 2003 Sep-Oct;10:457-467
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| Raj SM, Liu F. Engineering of RNase P ribozyme for gene-targeting applications. Gene 2003 Aug 14;313:59-69.
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| Sassone-Corsi P. Unique chromatin remodeling and transcriptional regulation in spermatogenesis. Science 2002;296:2176-2178.
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| RNA polymerase: www.rcsb.org/pdb/molecules/pdb40_1.html
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| Spliceosome: www.neuro.wustl.edu/neuromuscular/pathol/spliceosome.htm
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| Ribozyme: www.ribozyme.no/; highveld.com/pages/ribozyme.html
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| Thalassemia: www.cooleysanemia.org/; www.ygyh.org/thal/whatisit.htm
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