DSIF, A NOVEL TRANSCRIPTION ELONGATION-FACTOR THAT REGULATES RNA-POLYMERASE-II PROCESSIVITY, IS COMPOSED OF HUMAN SPT4 AND SPT5 HOMOLOGS

We report the identification of a transcription elongation factor from HeLa cell nuclear extracts that causes pausing of RNA polymerase II ( Pol II) in conjunction with the transcription inhibitor 5,6-dichloro-1 -beta-D-ribofuranosylbenzimidazole (DRB). This factor, termed (D) unde r bar RB (s) under bar ensitivity-(i) under bar nducing (f) under bar actor (DSIF), is also required for transcription inhibition by H8. DSI F has been purified and is composed of 160-kD (p160) and 14-kD (p14) s ubunits. Isolation of a cDNA encoding DSIF p160 shows it to be a homol og of the Saccharomyces cerevisiae transcription factor Spt5. Recombin ant Supt4h protein, the human homolog of yeast Spt4, is functionally e quivalent to DSIF p14, indicating that DSIF is composed of the human h omologs of Spt4 and Spt5. In addition to its negative role in elongati on, DSIF is able to stimulate the rate of elongation by RNA Pol II in a reaction containing limiting concentrations of ribonucleoside tripho sphates. A role for DSIF in transcription elongation is further suppor ted by the fact that p160 has a region homologous to the bacterial elo ngation factor NusG. The combination of biochemical studies on DSIF an d genetic analysis of Spt4 and Spt5 in yeast, also in this issue, indi cates that DSIF associates with RNA Pol II and regulates its processiv ity in vitro and in vivo.