We use the term "speckles" specifically to denote the interchromatin granule-related clusters of snRNP staining, and not the overall punctate pattern that includes diffuse nucleoplasmic staining and coiled bodies. The importance of speckles is still being debated; nonetheless, interchromatin granule speckles are genuine nuclear structures that can be visualized directly in the electron microscope. Speckles disperse when cells enter mitosis, but snRNPs and protein splicing factors reform into speckle-like structures during telophase, before their reimport into daughter nuclei. Thus, snRNP speckles can occur in the absence of DNA and transcription.

The mRNA from some highly transcribed genes is enriched near speckles, suggesting a possible role in mRNA transcription or maturation. However, speckles are not major sites of transcription, which occurs in thousands of foci throughout the nucleoplasm.

An alternative scenario is that speckles function either as depots supplying splicing factors to active gene loci, or way stations accumulating snRNPs bound either to partially spliced pre-mRNA or to excised introns after release of mRNA from the spliceosome.

The localization of splicing factors is dynamic and involves trafficking between nuclear substructures. It seems likely the mRNA precurors are transcribed and processed at active gene loci dispersed throughout the nucleoplasm and that snRNPs and other RNA processing factors cycle between these transcription sites and interchromatin granule speckles. Such cycling may be regulated by protein phosphorylation, because perturbation of both kinase and phosphatase activities can cause changes in the degree of punctate staining shown by splicing factors.

It remains to be established whether the interachromatin granule speckles simply store inactive factors or participate more actively in one or more steps connected with mRNA maturation and transport.

HeLa cells stained with antibodies to various proteins found in nuclear speckles:

Y12* (monoclonal antibody to a subset of Sm proteins) *Petterson, I., Hinterberger, M., Mimori, T., Gottlieb, E. and Steitz, J.A. (1984) J. Biol. Chem. 259:5907-5914.	4G3' (monoclonal antibody to U2 B" snRNP) 'Habets, W.J., Hoet, M.H., DeJong, B.A., Van der Kemp, A. and Van Venrooij, W.J. (1989) 143:2560-2566.	SC35"(monoclonal antibody to SR proteins) "Fu, X. and Maniatis, T. (1990) Nature 343:437-441.