Although many mRNAs are eventually degraded in P-bodies, some remain intact and are later returned to the pool of translating mRNAs. To be “rescued” in this way, mRNAs move from P-bodies to another type of aggregate known as a stress granule, which contains translation initiation factors, poly-A-binding protein, and small ribosomal subunits. Translation itself does not occur in stress granules, but mRNAs can become “translation-ready” as the proteins bound to them in P-bodies are replaced with those in stress granules. The movement of mRNAs between active translation, P-bodies, and stress granules can be seen as an mRNA cycle (Figure 7–73) where the competition between translation and mRNA degradation is carefully controlled. Thus, when translation initiation is blocked (by starvation, drugs, or genetic manipulation), stress granules enlarge as more and more nontranslated mRNAs are moved directly into them for storage. Clearly, once a cell has made the large investment in producing a properly processed mRNA molecule, it carefully controls its subsequent fate.
Many steps in the pathway from RNA to protein are regulated by cells in order to control gene expression. Most genes are regulated at multiple levels, in addition to being controlled at the initiation stage of transcription. The regulatory mechanisms include (1) attenuation of the RNA transcript by its premature termination, (2) alternative RNA splice-site selection, (3) control of 3ʹ-end formation by cleavage and poly-A addition, (4) RNA editing, (5) control of transport from the nucleus to the cytosol, (6) localization of mRNAs to particular parts of the cell, (7) control of translation initiation, and (8) regulated mRNA degradation. Most of these control processes require the recognition of specific sequences or structures in the RNA molecule being regulated, a task performed by either regulatory proteins or regulatory RNA molecules.
Figure 7–72 Visualization of P-bodies.
human cells were stained with antibodies to a component of the mrnA decapping enzyme Dcp1a (left panels) and to the Argonaute protein (middle panels). As described later in this chapter, Argonaute is a key component of rnA interference pathways. the merged image (right panels) shows that the two proteins co-localize to p-bodies in the cytoplasm. (Adapted from
J. liu et al., Nat. Cell Biol. 7:719–723, 2005. with permission from Macmillan publishers ltd.)
Figure 7–73 Possible fates of an mRNA molecule. An mrnA molecule released from the nucleus can be actively translated (center), stored in stress granules (right), or degraded in p-bodies (left). As the needs of the cell change, mrnAs can be shuffled from one pool to the next, as indicated by the arrows.
In the previous chapter, we introduced the central dogma, according to which the flow of genetic information proceeds from DNA through RNA to protein (Figure 6–1). But we have seen throughout this book that RNA molecules perform many critical tasks in the cell besides serving as intermediate carriers of genetic information. Among these noncoding RNAs are the rRNA and tRNA molecules, which are responsible for reading the genetic code and synthesizing proteins. The RNA molecule in telomerase serves as a template for the replication of chromosome ends, snoRNAs modify ribosomal RNA, and snRNAs carry out the major events of RNA splicing. And we saw in the previous section that Xist RNA has an important role in inactivating one copy of the X chromosome in females.
A series of recent discoveries has revealed that noncoding RNAs are even more prevalent than previously imagined. We now know that such RNAs play widespread roles in regulating gene expression and in protecting the genome from viruses and transposable elements. These newly discovered RNAs are the subject of this section.