COMPARTMENTALIZATION OF SPECIFIC PRE-MESSENGER-RNA METABOLISM - AN EMERGING VIEW

It is increasingly recognized that the mammalian interphase nucleus contains a number of non-membranous compartments in which macromolecules associated with different nuclear functions concentrate. This review focuses on the function of a major compartment consisting of domains highly enriched in pre-mRNA splicing components and poly (A) RNA, commonly identified by the splicing factor, SC-35, RNA synthesis, as judged by uridine incorporation, occurs throughout the nucleoplasm, primarily in the interdomain space. However, uridine labels several types of nuclear RNA, only a fraction of which is pre-mRNA, and such studies cannot address the question of whether specific genes are transcribed in specific places. Similarly, interpretations of transcriptional inhibition studies are compromised by the global impact that inhibition has on nuclear structure and function, and by conflicting results. Localization of specific protein coding genes or RNAs circumvents these limitations. For several sequences studied thus far, a non-random relationship to SC-35 domains has been observed, with most, but not all, active genes encoding intron-containing pre-mRNAs showing a very high degree of association. In some cases this was directly demonstrated to be the site of transcription and processing. Consistent with earlier uridine incorporation studies, we have found that transcription occurs at the outer edge of the SC-35 domain, likely corresponding to the border of ultrastructures termed interchromatin granule clusters. These preliminary glimpses into gene localization strongly argue for a sequence-specific spatial association of some transcriptionally active genes with SC-35 domains, and suggest an integrated functional organization of the genome with these nuclear compartments enriched in splicing factors and poly (A) RNA.