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Department of Pathology and * Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510
In the preceding study we found that Sm
snRNPs and SerArg (SR) family proteins co-immunoprecipitate with Pol II molecules containing a hyperphosphorylated CTD (). The association between Pol IIo and splicing factors is maintained
in the absence of pre-mRNA, and the polymerase need
not be transcriptionally engaged (). The
latter findings led us to hypothesize that a phosphorylated form of the CTD interacts with pre-mRNA splicing components in vivo. To test this idea, a nested set of CTD-derived proteins was assayed for the ability to alter the nuclear distribution of splicing factors, and to interfere with splicing in vivo. Proteins containing heptapeptides 1-52 (CTD52), 1-32 (CTD32), 1-26 (CTD26), 1-13 (CTD13), 1-6 (CTD6), 1-3 (CTD3), or
1 (CTD1) were expressed in mammalian cells. The
CTD-derived proteins become phosphorylated in vivo,
and accumulate in the nucleus even though they lack a
conventional nuclear localization signal. CTD52 induces a selective reorganization of splicing factors from discrete nuclear domains to the diffuse nucleoplasm, and significantly, it blocks the accumulation of
spliced, but not unspliced, human 
-globin transcripts.
The extent of splicing factor disruption, and the degree
of inhibition of splicing, are proportional to the number
of heptapeptides added to the protein. The above results indicate a functional interaction between Pol II's
CTD and pre-mRNA splicing.
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