NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation.
DRB is a classic inhibitor of transcription elongation by RNA polymerase II (pol II). Since DRB generally affects class II genes, factors involved in this process must play fundamental roles in pol II elongation. Recently, two elongation factors essential for DRB action were identified, namely DSIF and P-TEFb. Here we describe the identification and purification from HeLa nuclear extract of a third protein factor required for DRB-sensitive transcription. This factor, termed negative elongation factor (NELF), cooperates with DSIF and strongly represses pol II elongation. This repression is reversed by P-TEFb-dependent phosphorylation of the pol II C-terminal domain. NELF is composed of five polypeptides, the smallest of which is identical to RD, a putative RNA-binding protein of unknown function. This study reveals a molecular mechanism for DRB action and a regulatory network of positive and negative elongation factors.
Yamaguchi
Y
Y
Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
Takagi
T
T
Wada
T
T
Yano
K
K
Furuya
A
A
Sugimoto
S
S
Hasegawa
J
J
Handa
H
H
D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D004004:Dichlororibofuranosylbenzimidazole / Q000494:pharmacology; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors* / Q000235:genetics; D016601:RNA-Binding Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D035602:Transcriptional Elongation Factors; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C481011:SUPT4H1 protein, human; C112224:SUPT5H protein, human; D014157:Transcription Factors; D035602:Transcriptional Elongation Factors; C118437:negative elongation factor; D004004:Dichlororibofuranosylbenzimidazole; D042925:Positive Transcriptional Elongation Factor B; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II