Figure 7–3 Differences in RNA levels for two human genes in seven different tissues. to obtain the rnA data by the technique known as RNA-seq (see p. 447), rnA was collected from human cell lines grown in culture, derived from each of the seven indicated tissues. Millions of “sequence reads” were obtained and mapped across the human genome by matching rnA sequences to the DnA sequence of the genome. At each position along the genome, the height of the colored trace is proportional to the number of sequence reads that match the genome sequence at that point. As seen in the figure, the exon sequences in transcribed genes are present at high levels, reflecting their presence in mature mrnAs. intron sequences are present at much lower levels and reflect pre-mrnA molecules that have not yet been spliced plus intron sequences that have been spliced out but not yet degraded. (A) the gene coding for “all-purpose” actin, a major component of the cytoskeleton. note that the left-hand end of the mature β-actin mrnA is not translated into protein. As explained later in this chapter, many mrnAs have 5ʹ untranslated regions that regulate their translation into protein. (B) the same type of data displayed for the enzyme tyrosine aminotransferase, which is highly expressed in liver cells but not in the other cell types tested. (information for both panels from the University of California, Santa Cruz, Genome Browser (http://genome.ucsc.edu), which provides this type of information for every human gene. See also S. Djebali et al., Nature 489:101–108, 2012.) external Signals Can Cause a Cell to Change the expression of its Genes
Although the specialized cells in a multicellular organism have characteristic patterns of gene expression, each cell is capable of altering its pattern of gene expression in response to extracellular cues. If a liver cell is exposed to a glucocorticoid hormone, for example, the production of a set of proteins is dramatically increased. Released in the body during periods of starvation or intense exercise, glucocorticoids signal the liver to increase the production of energy from amino acids and other small molecules; the set of proteins whose production is induced includes the enzyme tyrosine aminotransferase, mentioned above. When the hormone is no longer present, the production of these proteins drops to its normal, unstimulated level in liver cells.
Other cell types respond to glucocorticoids differently. Fat cells, for example, reduce the production of tyrosine aminotransferase, while some other cell types do not respond to glucocorticoids at all. These examples illustrate a general feature of cell specialization: different cell types often respond very differently to the same extracellular signal. Other features of the gene expression pattern do not change and give each cell type its permanently distinctive character.
Gene expression Can Be regulated at Many of the Steps in the pathway from DnA to rnA to protein
If differences among the various cell types of an organism depend on the particular genes that the cells express, at what level is the control of gene expression exercised? As we saw in the previous chapter, there are many steps in the pathway leading from DNA to protein. We now know that all of them can in principle be regulated. Thus a cell can control the proteins it makes by (1) controlling when and how often a given gene is transcribed (transcriptional control), (2) controlling the splicing and processing of RNA transcripts (RNA processing control), (3) selecting which completed mRNAs are exported from the nucleus to the cytosol and determining where in the cytosol they are localized (RNA transport and localization control), (4) selecting which mRNAs in the cytoplasm are translated by ribosomes (translational control), (5) selectively destabilizing certain mRNA molecules in the cytoplasm (mRNA degradation control), or (6) selectively activating, inactivating, degrading, or localizing specific protein molecules after they have been made (protein activity control) (Figure 7–5).