THE NUCLEOLUS

Nucleoli are the sites of biosynthesis of the ribosomal precursors. Th ey contain may copies of the genes for the main rRNAs (18 S- and 28 S- rRNA) in the form of tandemly arranged repeats at the chromosomal nucl eolar organizer regions (NORs). They also contain the small rRNA (5S-r RNA) that is synthesized outside the nucleolus, specific nucleolar pro teins, among them the factors and enzymes necessary for transcription and transcript processing, and the precursor units of the ribosomes. I n man as in may vertebrate species, three main components of nucleoli, besides chromatin, can be detected: fibrillar centres (FC), dense fib rillar component (DCF), and granular component (GC). Within a nucleolu s the FCs are in many cases situated in its central region. The DFc fo rms a network of strands surrounding the FCs, but may sometimes reach for out towards the periphery of the nucleolus. The GC is usually situ ated in the peripheral regions of the nucleolus. In cells with a low l evel of ribosomal biosynthesis the nucleoli are small, usually with a single FC and little surrounding DFC and GC (''ring-shaped nucleolus'' ). In active cells the DFC forms a large network enclosing several, so metimes up to hundreds of FCs, and the GC covers a large area in the p eriphery (''compact nucleoli''). In cells at the onset of a new stimul ation, the DFC is very prominent whereas the FCs are few and small, an d the GC is also not very extensive (''reticulate nucleoli''). In some special cell types that are very active other arrangements of the str uctural components are found. In Sertoli cells, for instance, only one nucleolus is found, or occasionally two, each with a single large FC and a distinct area of GC, both areas being engulfed by DFC intermingl ed with some peripheral GC. Immunocytological and in situ hybridizatio n studies to localize the rRNA genes within the nucleolus have so far led to divergent results. Both fibrillar components, the FCs and the D FC, have been claimed as the most probable candiates. Transcription of rDNA and the subsequent early steps of ribosome biosynthesis are loca lized in the DFC, whereas later steps (mature rRNA, preribosomes) are localized in the GC. The FCs may also serve as sites for the preparati on of the rDNA for transcription, and as a store for certain nucleolar proteins. During mitosis, parts of the nucleolar proteins remain at t he NORs. A direct contact between the nucleolus and the nuclear envelo pe is frequently observed but is not dependent on nucleolar activity. The number of nucleoli per cell nucleus depends on the activity of the NORs and on the duration of the cell cycle. Intense activity combined with a long interphase leads to an association of the NORs and hence to a decrease in the number of nucleoli. In malignant cells, increased nucleoli are a sign of an increased ribosomal biogenesis, but need no t be directly related to the degree of malignancy.