the introns of other genes, especially those encoding ribosomal proteins. They are synthesized by RNA polymerase II and processed from excised intron sequences.
The Nucleolus Is a Ribosome-Producing Factory
The nucleolus is the most obvious structure seen in the nucleus of a eukaryotic cell when viewed in the light microscope. It was so closely scrutinized by early cytologists that an 1898 review could list some 700 references. We now know that the nucleolus is the site for the processing of rRNAs and their assembly into ribosome subunits. Unlike many of the major organelles in the cell, the nucleolus is not bound by a membrane (Figure 6–42); instead, it is a huge aggregate
Figure 6–41 Modifications of the precursor rRNA by guide RNAs. (A) Two prominent covalent modifications made to rRNA; the differences from the initially incorporated nucleotide are indicated by red atoms. Pseudouridine is an isomer of uridine; the base has been “rotated,” and is attached to the red C rather than to the red N of the sugar (compare to Figure 6–5B).
(B) As indicated, snoRNAs determine the sites of modification by base-pairing to complementary sequences on the precursor rRNA. The snoRNAs are bound to proteins, and the complexes are called snoRNPs (small nucleolar ribonucleoproteins). snoRNPs contain both the guide sequences and the enzymes that modify the rRNA.
Figure 6–42 electron micrograph of a thin section of a nucleolus in a human fibroblast, showing its three distinct zones. (A) View of entire nucleus.
Higher-power view of the nucleolus. It is believed that transcription of the rRNA genes takes place between the fibrillar center and the dense fibrillar component and that processing of the rRNAs and their assembly into the two subunits of the ribosome proceeds outward from the dense fibrillar component to the surrounding granular components. (Courtesy of E.G. Jordan and
J.
McGovern.)
Figure 6–43 Changes in the appearance of the nucleolus in a human cell during the cell cycle. Only the cell nucleus is represented in this diagram. In most eukaryotic cells, the nuclear envelope breaks down during mitosis, as indicated by the dashed circles.
of macromolecules, including the rRNA genes themselves, precursor rRNAs, mature rRNAs, rRNA-processing enzymes, snoRNPs, a large set of assembly factors (including ATPases, GTPases, protein kinases, and RNA helicases), ribosomal proteins, and partly assembled ribosomes. The close association of all these components allows the assembly of ribosomes to occur rapidly and smoothly.
Various types of RNA molecules play a central part in the chemistry and structure of the nucleolus, suggesting that it may have evolved from an ancient structure present in cells dominated by RNA catalysis. In present-day cells, the rRNA genes have an important role in forming the nucleolus. In a diploid human cell, the rRNA genes are distributed into 10 clusters, located near the tips of five different chromosome pairs (see Figure 4–11). During interphase, these 10 chromosomes contribute DNA loops (containing the rRNA genes) to the nucleolus; in
M phase, when the chromosomes condense, the nucleolus fragments and then disappears. Then, in the telophase part of mitosis, as chromosomes return to their semi-dispersed state, the tips of the 10 chromosomes reform small nucleoli, which progressively coalesce into a single nucleolus (Figure 6–43 and Figure 6–44). As might be expected, the size of the nucleolus reflects the number of ribosomes that the cell is producing. Its size therefore varies greatly in different cells and can change in a single cell, occupying 25% of the total nuclear volume in cells that are making unusually large amounts of protein.