Human Molecular Genetics, Vol 4, 1779-1789, Copyright © 1995 by Oxford University Press
PT Moen Jr, KP Smith and JB Lawrence
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
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.
REVIEWS
Compartmentalization of specific pre-mRNA metabolism: an emerging view
Department of Cell Biology, University of Massachusetts Medical School, Worcester 01655, USA.
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