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Gene Expression

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Biochemistry 2280A
Derek Mc Lachlin

Brandl Lecture 1 Notes: GENE EXPRESSION 11/07/2012 DNA – The Blueprint of Life – Fun Facts  Information is stored in DNA in the form of genes  The human genome encodes about 25,000 different protein encoding genes  In any one cell type, about 10,000 are expressed at various levels  The expression of the correct genes is essential for growth and differentiation of all cells Significance of Gene Expression  Many diseases are due to altered expression of one or more genes  Simple diseases involve often one gene, complex diseases often involve many genes  By manipulating gene expression, we have the potential to prevent or reverse disease The Central Dogma  DNA  RNA  PROTEIN  Two key steps: transcription (making RNA) and translation (making protein)  Why is there an RNA step in gene expression? Three main reasons include: 1. The RNA step provides an amplification which allows genes to be expressed at different levels 2. Because RNA can be easily degraded, expression of a gene can be stopped quickly 3. RNA provides additional opportunities to regulate the expression of genes Q: There are 2 steps at which genes can be regulated. True/False? ANS: False – there are many more than 2 steps Regulation of Gene Expression Steps at which gene expression can be regulated in a eucaryotic cell  Transcription o Initiation o Elongation o Termination  RNA processing o RNA editing o 5’ capping o Splicing o 3’ polyadenylation  mRNA export (movement of RNA from nucleus to cytoplasm for it to be expressed, occurs through nuclear pores – very important in coordinating gene expression)  Translation o Initiation o Elongation o Termination  mRNA degradation (amount of RNA is dependent on two factors – rate of synthesis and rate of decaying – can control amount of RNA in the cell by how rapidly it is degraded)  Protein modification (some proteins are synthesized in inactive form and require modification to become functional)  Protein degradation (level of protein also depends on rate of synthesis and rate of decaying) Q: Which step in a biological process is often the most highly regulated? ANS: The first step in a biological process is often highly regulated as it saves the energy required in the subsequent steps. If you regulate the last step, the cell would consume 2 ATP unnecessarily, whereas if you regulate the first step, you may not consume any ATP at all. Transcription – Significance  Because transcription is the first step in gene expression, it is often highly regulated  Many genes are principally controlled at the level of transcription  Many diseases result from defects in transcription factors (cancer)  The specificity of many transcription factors makes them logical drug targets First Focus on Prokaryotic Transcription  Mechanistically similar to eucaryotic transcription  But somewhat similar Terminology  Promoter – DNA sequences required to initiate transcription of a gene (or operon) o Bacterial promoter – promoter is almost always at the 5’ end  Operon – a set of genes transcribed from
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