FIGURE 10-1 Overview of RNA processing and post-transcriptional gene control. Nearly all cytoplasmic RNAs are processed from primary transcripts in the nucleus before they are exported to the cytoplasm. For protein-coding genes transcribed by RNA polymerase II, gene control can be exerted through step 1 the choice of alternative exons during pre-mRNA splicing and step 2 the choice of alternative poly(A) sites. Improperly processed mRNAs are blocked from export to the cytoplasm and degraded step 3 by a large complex called the exosome that contains multiple ribonucleases. Once the mRNA has been exported to the cytoplasm, step 4 translation initiation factors bind to the 5′ cap cooperatively with poly(A)-binding protein I bound to the poly(A) tail and initiate translation (see Figure 4-28). Step 5 mRNA is degraded in the cytoplasm by deadenylation and decapping followed by degradation by cytoplasmic exosomes. These processes occur rapidly in dense regions of the cytoplasm called P bodies that function in translational repression. The degradation rate of each mRNA is controlled, thereby regulating the mRNA concentration and, consequently, the amount of protein translated. Some mRNAs are synthesized without long poly(A) tails. Their translation is regulated by step 6 control of the synthesis of a long poly(A) tail by a cytoplasmic poly(A) polymerase. Step 7 Translation is also regulated by other mechanisms, including miRNAs. When expressed, these ~22-nucleotide RNAs inhibit translation of mRNAs to which they hybridize, usually in the 3′ untranslated region. tRNAs and rRNAs are also synthesized as precursor RNAs that must be step 8 processed before they are functional. Regions of precursors cleaved from the mature RNAs are degraded by nuclear exosomes step 9. See Houseley et al., 2006, Nat. Rev. Mol. Cell Biol. 7:529.