Nucleolar organizers are secondary constrictions within the mitotic chromosomes of eukaryotes. The primary constriction occurs at the centromere. The nucleolar organizer genetic locus contains tandemly repeated genes that encode the 42 S to 47 S precursor of ribosomal RNA (pre-rRNA) (see Nucleolus, Ribosomes). As the name implies, the nucleolar organizer gives rise to the nucleolus in the telophase of mitosis. During the late telophase, RNA polymerase I begins to transcribe rRNA genes once again, and the newly synthesized rRNA likely nucleates the assembly of the nucleolus by recruiting prenucleolar bodies to the transcription site.
Transcription of the 45 S rRNA genes is one of the primary events for nucleolar assembly. This was beautifully demonstrated by Karpen et al. (1), who inserted rRNA genes (ie, nucleolar organizers) within ectopic sites in Drosophila chromosomes by P-element-mediated integration. As a result, nucleoli were observed at ectopic sites of the polytene chromosomes. This work indicated that transcription of the ribosomal genes is necessary to initiate nucleolar assembly on the chromosome, but perhaps not sufficient. At least some of the nucleolar constituents used in the preceding interphase are retained in the cytoplasm during mitosis. In the late telophase, these constituents preassemble into extrachromosomal particles before or concomitant with the initiation of ribosomal gene transcription. These preassembled nucleolar particles, or prenucleolar bodies as they are called, contain at least the small nucleolar RNA, snoRNA U3, and the nucleolar proteins fibrillarin, nucleolin (C23), and NO38 (or B23) (2), all of which play a role in pre-rRNA processing. Although formation of the prenucleolar bodies is independent of transcription, fusion of the prenucleolar bodies to the organizer regions depends on rRNA transcription (3). Once the particles fuse with the nucleolar organizers, the resulting nucleoli grow in the early interphase because of increased rates of rRNA synthesis and the influx of other components necessary for ribosomal production (eg, ribosomal proteins). See Nucleolus for a more complete description of nucleolar structure and function.
Historically, Heitz (4) concluded that the number of secondary constrictions within certain chromosomes of Drosophila funebris is proportional to the number of nucleoli. He called these regions "sine acid thymonucleinico" (SAT, without DNA). It is now known that the mitotic nucleolar organizer regions retain a significant proportion of nucleolar-specific proteins relative to rDNA, as the chromosomes condense in prometaphase. These proteins include the RNA polymerase I complex, DNA topoisomerase I, and the transcription factors UBF and the SL1 complex (5). Together, these various proteins form a set that makes it possible to stain selectively for nucleolar organizers.
McClintock (6) actually coined the term "nucleolar organizer" to describe the satellite segment at the tip of maize chromosome 6 (the "nucleolar chromosome") that organizes the assembly of the nucleolus beginning in the telophase. If the terminal satellite element of chromosome 6 is broken into two equal portions by X-rays, her studies demonstrated that each portion gives rise to a nucleolus of normal size. McClintock’s observation suggests that not all ribosomal genes within the normal nucleolus may be active. Subsequent work with Drosophila (7, 8) and Xenopus (9) established that the tandemly repeated ribosomal genes reside at these nucleolar organizer regions. Nucleolar organizers occur on one or as many as six chromosomes, depending on the organism (10). Nucleolar gene clusters have been found on autosomes in some organisms and on sex chromosomes in others (eg, the X- and Y-chromosomes of Drosophila). Interestingly, ribosomal gene clusters are often found near telomeres on the shorter arm of the chromosomes that normally carry the nucleolar organizers. One possibility for this close association between the telomere and the nucleolar organizer is to reduce the adverse phenotypic affects of unequal crossing over between repeated rRNA genes on nonhomologous chromosomes (11, 12). Nucleolar organizers are found in humans on chromosomes 13, 14, 15, 21, and 22. All are acrocentric chromosomes.
