Narita Takashi, Yung Tetsu M C, Yamamoto Junichi, Tsuboi Yasunori, Tanabe Hideyuki, Tanaka Kiyoji, Yamaguchi Yuki, Handa Hiroshi
Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Yokohama, Kanagawa 226-8501, Japan.
Mol Cell. 2007 May 11;26(3):349-65. doi: 10.1016/j.molcel.2007.04.011.
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.
负性延伸因子（NELF）是一种由四个亚基组成的转录延伸因子，它与从神经疾病到癌症等多种疾病有关。我们在此表明，NELF与核帽结合复合体（CBC）相互作用，CBC是一种多功能因子，在多个mRNA加工步骤中发挥重要作用，这两种因子共同参与依赖复制的组蛋白mRNA的3'端加工，最有可能是通过与组蛋白茎环结合蛋白（SLBP）结合。引人注目的是，缺乏NELF和CBC会导致多聚腺苷酸化组蛋白mRNA的异常产生。此外，NELF与组蛋白基因位点在物理上相关联，并形成我们称为NELF体的独特核内焦点，这些焦点常与卡哈尔体和切割体重叠。我们的结果指出了NELF在组蛋白mRNA 3'端加工中的惊人作用，也表明NELF是一种在转录过程中协调不同mRNA加工步骤的新因子。
