Chen Y, Sinha K, Perumal K, Gu J, Reddy R
Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Biol Chem. 1998 Dec 25;273(52):35023-31. doi: 10.1074/jbc.273.52.35023.
Human signal recognition particle (SRP) RNA is transcribed by RNA polymerase III and terminates with -GUCUCUUUUOH on its 3' end. Our previous studies showed that the three terminal uridylic acid residues of human SRP RNA are post-transcriptionally removed and a single adenylic acid residue is added, resulting in a 3' end sequence of -GUCUCUAOH (Sinha, K. M., Gu, J., Chen, Y., and Reddy, R. (1998) J. Biol. Chem. 273, 6853-6859). In this study we show that the Alu RNA, corresponding to the 5' and 3' ends of SRP RNA, is also accurately processed and adenylated in vitro. Alu RNAs containing 7 or 11 additional nucleotides on the 3' end were accurately processed and then adenylated. Deletion analysis showed that an 87-nucleotide-long motif comprising of the 5' and 3' ends, including stem IV of the Alu RNA, is sufficient and necessary for the 3' end processing and adenylation. A 73-nucleotide-long construct with deletion of stem IV, required for the binding of SRP 9/14-kDa proteins, was neither processed nor adenylated. The adenylated Alu RNA as well as adenylated SRP RNA were bound to the SRP 9/14-kDa heterodimer and were immunoprecipitated by specific antibodies. A significant fraction of SRP RNA in the nucleoli was found to be processed and adenylated. These data are consistent with nascent SRP and/or Alu RNAs first binding to SRP 9/14-kDa protein heterodimer, followed by the removal of extra sequence on the 3' end and then the addition of one adenylic acid residue in the nucleus, before transport into the cytoplasm.
人类信号识别颗粒(SRP)RNA由RNA聚合酶III转录,其3'端以-GUCUCUUUUOH终止。我们之前的研究表明,人类SRP RNA的三个末端尿苷酸残基在转录后被去除,并添加了一个单腺苷酸残基,导致3'端序列为-GUCUCUAOH(辛哈,K.M.,顾,J.,陈,Y.,和雷迪,R.(1998年)《生物化学杂志》273,6853-6859)。在本研究中,我们表明,与SRP RNA的5'和3'端相对应的Alu RNA在体外也能被精确加工并腺苷酸化。在3'端含有7个或11个额外核苷酸的Alu RNA被精确加工,然后腺苷酸化。缺失分析表明,一个由5'和3'端组成的87个核苷酸长的基序,包括Alu RNA的茎IV,对于3'端加工和腺苷酸化是充分且必要的。一个缺失了SRP 9/14-kDa蛋白结合所需的茎IV的73个核苷酸长的构建体既没有被加工也没有被腺苷酸化。腺苷酸化的Alu RNA以及腺苷酸化的SRP RNA与SRP 9/14-kDa异二聚体结合,并被特异性抗体免疫沉淀。发现核仁中相当一部分SRP RNA被加工并腺苷酸化。这些数据与新生的SRP和/或Alu RNA首先与SRP 9/14-kDa蛋白异二聚体结合,随后在细胞核中去除3'端的额外序列,然后添加一个腺苷酸残基,再转运到细胞质中是一致的。