9 March 2005

Lecture 25

Reading: Chapter 8

A. Protein synthesis (The Central Dogma)

B. Genomes

C. Gene regulation

The activity, i.e. transcription, of genes is highly regulated. In our discussion, we will put genes into three categories based on their regulation: constitutive genes, inducible genes, and silenced genes. Constitutive genes are those that are always active. Genes for ribosomes are an example. They are constantly being transcribed because ribosomes are constantly needed for protein synthesis. Inducible genes are those that have variable activity, depending on the needs of the cell. For example, the glucose transporter proteins that muscle cells produce in response to insulin are the product of inducible genes. Insulin stimulates their activity. Silenced genes are those that have been permanently turned off. For example, some genes needed for nerve cell function will be silenced in muscle cells. Gene silencing is part of the process of cells aquiring their different identities.

1. Promoters and transcriptional regulation

Genes have different parts. The sequence of bases that codes for amino acids in a protein is just one of these. Another part of all genes is the promoter. This is a segment of DNA upstream from the region that is transcribed into messenger RNA. It is the part of the gene where RNA polymerase binds and begins copying the gene sequence into messenger RNA.

Transcription of genes is controlled by proteins that bind on or near the promoter. Some proteins will favor the binding of RNA polymerase and thereby transcription of the gene. Other proteins will prevent the binding of RNA polymerase and thus prevent transcription of the gene. These proteins are called "gene regulatory proteins" . (You will see them called transcription factors and regulatory proteins in your text and there are many other names for them, depending on what the protein does. We will call them all "gene regulatory proteins"). Gene regulatory proteins are coded for by "regulatory genes". Gene regulatory proteins often bind to more than one gene, which means that a regulatory gene can simultaneously govern the activity of sets of genes.

Some gene regulatory proteins bind to places other than the promoter of a gene but still affect its transcription. For example, some proteins bind to "enhancers", which are regions of DNA that are hundreds of bases upstream from the promoter. It is thought that these regions may loop around so that they interact with the promoter and improve binding of RNA polymerase for transcription.

2. Introns, exons, and alternative splicing

Within the region of a gene that is transcribed into messenger RNA, there are segments of DNA that do not code for amino acid sequence. These segments are called "introns", which is short for "intervening sequences". The parts of the gene sequence that do get translated into amino acid sequence are called "exons". Exons and introns alike are copied into messenger RNA by RNA polymerase but the introns are cut out by editing enzymes before the messenger RNA leaves the nucleus. The intron sequences are cut out of the messenger RNA molecule and the exons are spliced together.

Sometimes, exons from a gene are spliced together in several different ways, leading to different kinds of proteins. This process is called "alternative splicing". Alternative splicing is a means by which genes can be regulated after transcription occurs. It is also a way for cells to make more proteins than they have genes. As protein synthesis was being studied, a hypothesis was proposed that one gene coded for one protein. This is generally true but alternative splicing is one exception to this rule.