Aaaaaa

Exosome proteins have been found to bind to these 3' AU-rich sequences. Recent experiments suggest that the bound proteins interact with a deadenylating enzyme and with the exosome, thereby promoting the rapid deadenylation and subsequent 3' ^ 5' degradation of these mRNAs. In this mechanism, the rate of mRNA degradation is uncoupled from the frequency of translation. Thus mRNAs containing the AUUUA sequence can be translated at high frequency, yet also degraded rapidly, allowing the encoded proteins to be expressed in short bursts.

As shown in Figure 12-29, some mRNAs are degraded in pathways that do not involve significant deadenylation. In one of these, mRNAs are decapped before the poly(A) tail is shortened extensively. It appears that certain mRNA sequences make the cap sensitive to the decapping enzyme, but the precise mechanism is unclear. In the other alternative pathway, mRNAs first are cleaved internally by endonucle-ases. The RNA-induced silencing complex (RISC) discussed earlier is an example of such an endonuclease (see Figure 12-27). The fragments generated by internal cleavage then are degraded by exonucleases.

An Iron-Sensitive RNA-Binding Protein Regulates mRNA Translation and Degradation

Control of intracellular iron concentrations by the iron-response element-binding protein (IRE-BP) is an elegant example of a single protein that regulates the translation of one mRNA and the degradation of another. When intracellular iron stores are low, this dual control system operates to increase the level of free iron ions available for iron-requiring enzymes; when iron is in excess, the system operates to prevent accumulation of toxic levels of free ions. It is one of the simplest and best-understood examples of protein-mediated translational control.

One component in this system is the regulation of production of ferritin, an intracellular iron-binding protein. The 5' untranslated region of ferritin mRNA contains iron-response elements (IREs) that have a stem-loop structure. IRE-BP recognizes five specific bases in the IRE loop and the duplex nature of the stem. At low iron concentrations, IRE-BP is in an active conformation that binds to the IREs (Figure 12-30a). The bound IRE-BP blocks the 40S ribosomal subunit from scanning for the AUG start codon (see Figure 4-25), thereby inhibiting translation initiation. The resulting decrease in ferritin means less iron is complexed with the ferritin and is therefore available to iron-requiring enzymes. At high iron concentrations, IRE-BP is in an inactive conformation that does not bind to the 5' IREs, so translation initiation can proceed. The newly synthesized ferritin then binds free iron ions, preventing their accumulation to harmful levels.

The other part of this regulatory system controls the import of iron into cells. In vertebrates, ingested iron is carried through the circulation bound to a protein called transferrin. After binding to the transferrin receptor (TfR) in the plasma membrane, the transferrin-iron complex is brought into cells

(a) Ferritin mRNA IREs

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment