Figure 6–38 Schematic illustration of an export-ready mRNA molecule and its transport through the nuclear pore.
As indicated, some proteins travel with the mRNA as it moves through the pore, whereas others remain in the nucleus. The nuclear export receptor for mRNAs is a complex of proteins that binds to an mRNA molecule once it has been correctly spliced and polyadenylated. After the mRNA has been exported to the cytosol, this export receptor dissociates from the mRNA and is re-imported into the nucleus, where it can be used again. The final check indicated here, called nonsense-mediated decay, will be described later in the chapter.
out in small clusters on five different chromosomes (see Figure 4–11), while cells of the frog Xenopus contain about 600 rRNA gene copies per haploid genome in a single cluster on one chromosome (Figure 6–39).
There are four types of eukaryotic rRNAs, each present in one copy per ribosome. Three of the four rRNAs (18S, 5.8S, and 28S) are made by chemically modifying and cleaving a single large precursor rRNA (Figure 6–40); the fourth (5S RNA) is synthesized from a separate cluster of genes by a different polymerase, RNA polymerase III, and does not require chemical modification.
Extensive chemical modifications occur in the 13,000-nucleotide-long precursor rRNA before the rRNAs are cleaved out of it and assembled into ribosomes. These include about 100 methylations of the 2ʹ-OH positions on nucleotide sugars and 100 isomerizations of uridine nucleotides to pseudouridine (Figure 6–41A). The functions of these modifications are not understood in detail, but they probably aid in the folding and assembly of the final rRNAs, or subtly alter the function of ribosomes. Each modification is made at a specific position in the precursor rRNA, specified by “guide RNAs,” which position themselves on the precursor rRNA through base-pairing and thereby bring an RNA-modifying enzyme to the appropriate position (Figure 6–41B). Other guide RNAs promote cleavage of the precursor rRNAs into the mature rRNAs, probably by causing conformational changes in the precursor rRNA that expose these sites to nucleases. All of these guide RNAs are members of a large class of RNAs called small nucleolar RNAs (or snoRNAs), so named because these RNAs perform their functions in a sub-compartment of the nucleus called the nucleolus. Many snoRNAs are encoded in 13,000 nucleotides degraded regions of nucleotide sequence
CLEAVAGE 5.8S rRNA 28S rRNA 5S rRNA made elsewhere incorporated into large ribosomal subunit
Figure 6–39 Transcription from tandemly arranged rRNA genes, as seen in the electron microscope. The pattern of alternating transcribed gene and nontranscribed spacer is readily seen.  A higher-magnification view of rRNA genes is shown in Figure 6–10. (From V.E. Foe, Cold Spring Harb. Symp. Quant. Biol. 42:723–740, 1978. With permission from Cold Spring Harbor Laboratory Press.)
Figure 6–40 The chemical modification and nucleolytic processing of a eukaryotic 45S precursor rRNA molecule into three separate ribosomal RNAs.
Two types of chemical modifications (color-coded as indicated in Figure 6–41) are made to the precursor rRNA before it is cleaved. Nearly half of the nucleotide sequences in this precursor rRNA are discarded and degraded in the nucleus by the exosome. The rRNAs are named according to their “S” values, which refer to their rate of sedimentation in an ultracentrifuge. The larger the S value, the larger the rRNA.