Post-Transcriptional Controls PDF

POST-TRANSCRIPTIONAL CONTROLS We have seen that transcription regulators control gene expression by promoting or hindering the transcription of specific genes. The vast majority of genes in all organisms are regulated in this way. But many additional points of control can come into play later in the...

POST-TRANSCRIPTIONAL CONTROLS We have seen that transcription regulators control gene expression by promoting or hindering the transcription of specific genes. The vast majority of genes in all organisms are regulated in this way. But many additional points of control can come into play later in the pathway from DNA to protein, giving cells a further opportunity to adjust the amount or activity of the gene products that they make (see Figure 8–3). These post-transcriptional controls, which operate after transcription has begun, play a crucial part in further fine-tuning the expression of almost all genes; for some genes, they are the primary means of regulation. We have already encountered a few examples of such posttranscriptional control. For example, alternative RNA splicing allows different forms of a protein, encoded by the same gene, to be made in different tissues (Figure 7–25). And we saw that various post-translational modifications of a protein can regulate its concentration and activity (see Figure 4–45). In the remainder of this chapter, we consider several other examples—some only recently discovered—of the many ways in which cells can manipulate the expression of a gene after transcription has commenced. mRNAs Contain Sequences That Control Their Translation https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/132!/4?lti=true&control=control-toc 10/12/23, 8:50 PM Page 1 of 34 We saw in Chapter 7 that an mRNA’s life span is dictated by specific nucleotide sequences within the untranslated regions that lie both upstream and downstream of the protein-coding sequence. These sequences often contain binding sites for proteins that are involved in RNA degradation. But they also carry information specifying whether—and how often—the mRNA is to be translated into protein. Although the details differ between eukaryotes and bacteria, the general strategy is similar for both. Bacterial mRNAs contain a short ribosome-binding sequence located a few nucleotide pairs upstream of the AUG codon where translation begins (see Figure 7–42). This binding sequence forms base pairs with the rRNA in the small ribosomal subunit, correctly positioning the initiating AUG codon within the ribosome. Because this interaction is needed for efficient translation initiation, it provides an ideal target for translational control. By blocking—or exposing—the ribosomebinding sequence, the bacterium can either inhibit (or promote) the translation of an mRNA (Figure 8–25). https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/132!/4?lti=true&control=control-toc 10/12/23, 8:50 PM Page 2 of 34 (A) (B) https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/132!/4?lti=true&control=control-toc 10/12/23, 8:50 PM Page 3 of 34 Figure 8–25 A bacterial gene’s expression can be controlled by regulating translation of its mRNA. (A) Sequence-specific RNA-binding proteins can repress the translation of specific mRNAs by keeping the ribosome from binding to the ribosome-binding sequence (orange) in the mRNA. Some bacteria exploit this mechanism to inhibit the translation of ribosomal proteins. If a ribosomal protein is accidentally produced in excess over other ribosomal components, the free protein will inhibit translation of its own mRNA, thereby blocking its own synthesis. As new ribosomes are assembled, the levels of the free protein decrease, allowing the mRNA to again be translated and the ribosomal protein to be produced. In this way, the cell balances the levels of its ribosomal proteins, ensuring that no single protein is under- or oversupplied. (B) An mRNA from the pathogen Listeria monocytogenes contains a “thermosensor” RNA sequence that controls the translation of a set of mRNAs that code for proteins the bacterium needs to successfully infect its host. At the warmer temperatures inside a host, base pairs within the thermosensor come apart, exposing the ribosomebinding sequence, so the necessary protein is made. In eukaryotes, specialized repressor proteins can similarly inhibit translation initiation by binding to specific nucleotide sequences in the 5′ untranslated region of the mRNA, thereby preventing the ribosome from finding the first AUG. When conditions change, the cell can inactivate the repressor to initiate translation of the mRNA. Regulatory RNAs Control the Expression of Thousands of Genes As we saw in Chapter 7, RNAs perform many critical biological tasks. In addition to the mRNAs, which encode proteins, noncoding RNAs have a variety of functions. Some, such as transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), play key structural and catalytic roles in the cell, particularly in protein synthesis. And the RNA component of telomerase is crucial for the complete duplication of eukaryotic chromosomes (see Figure 6–23). But we now know that many organisms, particularly animals and plants, produce thousands of additional noncoding RNAs. https://nerd.wwnorton.com/nerd/231302/r/goto/cfi/132!/4?lti=true&control=control-toc 10/12/23, 8:50 PM Page 4 of 34