DRB sensitivity-inducing factor complex (DSIF complex, DSIF)

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 Structure: - consists of subunits SUPT4H1 & SUPT5H.

General

molecular complex transferase

Properties

MOTIF: active site SUBUNITS: transcription elongation factor SPT5 MOTIF: glutamate-rich region {11-106} MOTIF: glutamate residue (SEVERAL) binding site SITE: 176-270 FOR-BINDING-OF: transcription elongation factor SPT4 KOW 1 {273-306} RNA pol-2 interaction {313-420} KOW 2 {420-451} KOW 3 {472-503} KOW 4 {594-627} Ser phosphorylation site {S666} KOW 5 {704-737} MOTIF: Thr phosphorylation site {T709} Tyr phosphorylation site {Y717} CTR1 {754-817} MOTIF: G- S-[QR]-T-P-X-[YQ] {754-817} (9) Thr phosphorylation site {T775} Thr phosphorylation site {T784} CTR2 NAME: CTR2 SITE: 844-968 MOTIF: proline residue (SEVERAL) P-[TS]-P-S-P-[QA]-[SG]-Y (10) Thr phosphorylation site {T1034} transcription elongation factor SPT4 COMPARTMENT: cell nucleus MOTIF: binding site SITE: 1-40 FOR-BINDING-OF: transcription elongation factor SPT5 MOTIF: Zn finger C4-type SITE: 16-36 EFFECTOR-BOUND: Zn+2

References

UniProt :accession O00267

Components

transcription elongation factor SPT4; hSPT4; DRB sensitivity-inducing factor small subunit; DSIF small subunit; DSIF p14 (SUPT4H1, SPT4H, SUPT4H) transcription elongation factor SPT5; hSPT5; DRB sensitivity-inducing factor large subunit; DSIF large subunit; DSIF p160; Tat-cotransactivator 1 protein; Tat-CT1 protein (SUPT5H, SPT5, SPT5H)