Interpreting nucleolar structure: where are the transcribing genes?

The nucleolus, the site of ribosomal RNA synthesis, provides us with one of the best opportunities for unravelling the relationships between transcription and the spatial organization of chromatin. Some of the. best visualizations of the transcription process have come from nucleolar spread preparations (Miller, 1981) but this procedure introduces major structural reorganizations that deny us a molecular interpretation of the intact nucleolus. The fine structure of nucleoli can be described in terms of the distribution of three basic components together with condensed chromatin and nucleolar spaces of various sizes called interstices or vacuoles (Fig. 1). There is general agreement concerning the description and identification of the three basic components (Jordan, 1984). They are the fibrillar centres, the dense fibrillar component, and the granular component. However, their explanation in molecular terms is still unclear. General agreement exists on the view that the three components correspond in some way to the different events in the transcription and processing of rRNA into RNP. The problem arises in assigning functions to particular nucleolar components. Disagreement begins with the fundamental process of rRNA gene transcription. Some argue that this is restricted to the fibrillar centre while others believe it occurs in the dense fibrillar component. It is the view of the author that even the granular component should not be dismissed as a candidate. With this uncertainty it might be helpful to outline all possible interpretations of nucleolar structure. To this end seven different schemes are presented (Fig. 2). Three of the schemes, essentially encompassing the major differences in interpretation, have been drawn out in more detail (Fig. 3).