DRB sensitivity-inducing factor complex (DSIF complex, DSIF)
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Function
- regulates mRNA processing & transcription elongation by RNA polymerase 2
- regulates mRNA capping by stimulating mRNA guanylyltransferase activity of RNGTT.
- acts cooperatively with NELF complex to enhance transcriptional pausing at sites proximal to the promoter
- transcriptional pausing may facilitate assembly of elongation competent RNA polymerase 2
- DSIF & NELF inhibit transcription elongation factor TFIIS
- TFIIS binds to RNA polymerase 2 at transcription pause sites & stimulates its weak intrinsic nuclease activity
- cleavage of blocked transcripts by RNA polymerase 2 promotes resumption of transcription from the new 3' terminus & may allow repeated attempts at transcription through natural pause sites
- DSIF can also upregulate transcriptional elongation
- required for efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat
- DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR & blocks premature release of HIV-1 transcripts at terminator sequences
- DSIF interacts with P-TEFb complex
- DSIF interacts with RNA polymerase 2, & this interaction is diminished by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb
- DSIF also interacts with the NELF complex; interaction occurs following prior binding of DSIF to RNA polymerase 2
- DSIF also interacts with HRMT1L2/PRMT1, HTATSF1/TATSF1, RNGTT/CAP1A, SKB1/PRMT5, SUPT6H, & can interact with PIN1