HIV-1 Tat binds human CyclinT1 and recruits the CDK9/P-TEFb complex to the viral 
TAR RNA in a step that links RNA polymerase II (RNAPII) C-terminal domain (CTD) 
Ser 2 phosphorylation with transcription elongation. Previous studies have 
suggested a connection between Tat and pre-mRNA splicing factors. Here we show 
that the splicing-associated c-Ski-interacting protein, SKIP, is required for 
Tat transactivation in vivo and stimulates HIV-1 transcription elongation, but 
not initiation, in vitro. SKIP associates with CycT1:CDK9/P-TEFb and Tat:P-TEFb 
complexes in nuclear extracts and interacts with recombinant Tat:P-TEFb:TAR RNA 
complexes in vitro, indicating that it may act through nascent RNA to overcome 
pausing by RNAPII. SKIP also associates with U5snRNP proteins and tri-snRNP110K 
in nuclear extracts, and facilitates recognition of an alternative Tat-specific 
splice site in vivo. The effects of SKIP on transcription elongation, binding to 
P-TEFb, and splicing are mediated through the SNW domain. HIV-1 Tat 
transactivation is accompanied by the recruitment of P-TEFb, SKIP, and 
tri-snRNP110K to the integrated HIV-1 promoter in vivo, whereas the U5snRNPs 
associate only with the transcribed coding region. These findings suggest that 
SKIP plays independent roles in transcription elongation and pre-mRNA splicing.