NELF interacts with CBC and participates in 3' end processing of replication-dependent histone mRNAs.
Negative elongation factor (NELF) is a four subunit transcription elongation factor that has been implicated in numerous diseases ranging from neurological disorders to cancer. Here we show that NELF interacts with the nuclear cap binding complex (CBC), a multifunctional factor that plays important roles in several mRNA processing steps, and the two factors together participate in the 3' end processing of replication-dependent histone mRNAs, most likely through association with the histone stem-loop binding protein (SLBP). Strikingly, absence of NELF and CBC causes aberrant production of polyadenylated histone mRNAs. Moreover, NELF is physically associated with histone gene loci and forms distinct intranuclear foci that we call NELF bodies, which often overlap with Cajal bodies and cleavage bodies. Our results point to a surprising role of NELF in the 3' end processing of histone mRNAs and also suggest that NELF is a new factor that coordinates different mRNA processing steps during transcription.
Narita
Takashi
T
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama, Kanagawa 226-8501, Japan.
Yung
Tetsu M C
TM
Yamamoto
Junichi
J
Tsuboi
Yasunori
Y
Tanabe
Hideyuki
H
Tanaka
Kiyoji
K
Yamaguchi
Yuki
Y
Handa
Hiroshi
H
D005786:Gene Expression Regulation / Q000235:genetics; D006367:HeLa Cells; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D039502:Nuclear Cap-Binding Protein Complex / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D011485:Protein Binding; D021122:Protein Subunits; D026721:RNA 3' End Processing / Q000235:genetics*; D012315:RNA Caps; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism
D006657:Histones; D039502:Nuclear Cap-Binding Protein Complex; D009687:Nuclear Proteins; D039102:Poly(A)-Binding Proteins; D021122:Protein Subunits; D012315:RNA Caps; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C092663:SLBP protein, human; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; C118437:negative elongation factor