Once a newly made eukaryotic mRNA molecule has passed through a nuclear pore and entered the cytosol, it is typically met by ribosomes, which translate it into a polypeptide chain (see Figure 6–8). Once the first round of translation “passes” the nonsense-mediated decay test (see Figure 6–76), the mRNA is usually translated in earnest. If the mRNA encodes a protein that is destined to be secreted or expressed on the cell surface, a signal sequence at the protein’s N-terminus will direct it to the endoplasmic reticulum (ER). In this case, as discussed in Chapter 12, components of the cell’s protein-sorting apparatus recognize the signal sequence as soon as it emerges from the ribosome and direct the entire complex of ribosome, mRNA, and nascent protein to the membrane of the ER, where the remainder of the polypeptide chain is synthesized. In other cases, free ribosomes in the cytosol synthesize the entire protein, and signals in the completed polypeptide chain may then direct the protein to other sites in the cell.
Many mRNAs are themselves directed to specific intracellular locations before their efficient translation begins, allowing the cell to position its mRNAs close to the sites where the encoded protein is needed. RNA localization has been observed in many organisms, including unicellular fungi, plants, and animals, and it is likely to be a common mechanism that cells use to concentrate high-level production of proteins at specific sites. This strategy also provides the cell with other advantages. For example, it allows the establishment of asymmetries in the cytosol of the cell, a key step in many stages of development. Localized mRNA, coupled with translational control, also allows the cell to regulate gene expression independently in different regions. This feature is particularly important in large, highly polarized cells such as neurons, where it plays a central role in synaptic function.
Several mechanisms for mRNA localization have been discovered (Figure 7–64), all of which require specific signals in the mRNA itself. These signals are usually concentrated in the 3ʹ untranslated region (UTR), the region of RNA that
Figure 7–64 Mechanisms for the localization of mRNAs. the mrnA to be localized leaves the nucleus through nuclear pores (top). Some localized mrnAs (left diagram) travel to their destination by associating with cytoskeletal motors, which use the energy of Atp hydrolysis to move the mrnAs unidirectionally along filaments in the cytoskeleton (red) (see Chapter 16). At their destination, the mrnAs are held in place by anchor proteins (black). Other mrnAs randomly diffuse through the cytosol and are simply trapped by anchor proteins and at their sites of localization (center diagram). Some mrnAs (right diagram) are degraded in the cytosol unless they have bound, through random diffusion, a localized protein complex that anchors and protects the mrnA from degradation (black). each mechanism requires specific signals on the mrnA, which are typically located in the 3ʹ Utr. Additional components can block the translation of the mrnA until it is properly localized. (Adapted from h.D. lipshitz and C.A. Smibert, Curr. Opin. Genet. Dev. 10:476–488, 2000. with permission from elsevier.)