RNA travel: tracks from DNA to cytoplasm.

Is There a Spatial Component to Nuclear RNA Processing and Transport? A controversial model holds that the RNA processing machinery resides at defined locations in the nucleus and that RNA transcripts travel on defined paths through these sites on their route to the cytoplasm. Thus, transcription, processing, and transport into the cytoplasm would occur in an ordered fashion as transcripts move from the gene to the nuclear pores. The spatial features of this model are analogous to the movement of a newly synthesized polypeptide through the cytoplasmic secretion machinery. The processing machinery (signal peptidase, glycosyl transferases, etc.) resides at defined locations, and the polypeptide to be secreted is transported from place to place (Pryor et al., 1992). This transport model makes two predictions. First, the components involved in these nuclear processes, e.g., active RNA polymerase II, splicing components, and nuclear pores, should have different and defined locations, perhaps sequentially distal from the location of the genes. Second, the steady-state distribution of nuclear transcripts (in flagrante transporto) might be nonuniform, reflecting a defined route between processing stations or between the active gene and the nuclear periphery. These predictions are supported by some studies, but also contradicted by other studies. We present both sidesof this interesting controversy in the hope of stimulating critical thinking about how RNA is transported from its site of synthesis to the cytoplasm. Speckles, Foci, and Tracks In support of the prediction that nuclear components reside at defined locations is the notable concentration of splicing components in a number of discrete light microscopic subnuclear domains, termed speckles and foci (e.g., Spector et al., 1991; Carmo-Fonseca et al., 1992). Although different in a number of ways, both nuclearstructures have been previously defined at the electron microscopic level; the larger, more intense speckles are probably interchromatin granules, and foci are coiled bodies. In support of the prediction that transcripts follow a defined route, is the description of nuclear transcript tracks or pathways from an Epstein-Barr virus-transformed cell line (Lawrence et al., 1969)orfrom aserum-induced c-fosgene (Huang and Spector, 1991). Taken together, it is tempting to draw a simple cell biological picture: pre-mRNA is spliced in speckles (and perhaps also in foci), and then the fully processed transcripts are transported along tracks Minireview