Liu Yingmiao, Kuersten Scott, Huang Tao, Larsen Alison, MacMorris Margaret, Blumenthal Thomas
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Denver, Colorado 80262, USA.
RNA. 2003 Jun;9(6):677-87. doi: 10.1261/rna.2128903.
Polycistronic pre-mRNAs from Caenohabditis elegans operons are processed by internal cleavage and polyadenylation to create 3' ends of mature mRNAs. This is accompanied by trans-splicing with SL2 approximately 100 nucleotides downstream of the 3' end formation sites to create the 5' ends of downstream mRNAs. SL2 trans-splicing depends on a U-rich element (Ur), located approximately 70 nucleotides upstream of the trans-splice site in the intercistronic region (ICR), as well as a functional 3' end formation signal. Here we report the existence of a novel gene-length RNA, the Ur-RNA, starting just upstream of the Ur element. The expression of Ur-RNA is dependent on 3' end formation as well as on the presence of the Ur element, but does not require a trans-splice site. The Ur-RNA is not capped, and alteration of the location of the Ur element in either the 5' or 3' direction alters the location of the 5' end of the Ur-RNA. We propose that a 5' to 3' exonuclease degrades the precursor RNA following cleavage at the poly(A) site, stopping when it reaches the Ur element, presumably attributable to a bound protein. Part of the function of this protein can be performed by the MS2 coat protein. Recruitment of coat protein to the ICR in the absence of the Ur element results in accumulation of an RNA equivalent to Ur-RNA, and restores trans-splicing. Only SL1, however, is used. Therefore, coat protein is sufficient for blocking the exonuclease and thereby allowing formation of a substrate for trans-splicing, but it lacks the ability to recruit the SL2 snRNP. Our results also demonstrate that MS2 coat protein can be used as an in vivo block to an exonuclease, which should have utility in mRNA stability studies.
秀丽隐杆线虫操纵子的多顺反子前体mRNA通过内部切割和多聚腺苷酸化进行加工,以形成成熟mRNA的3'末端。这伴随着在3'末端形成位点下游约100个核苷酸处与SL2进行反式剪接,以形成下游mRNA的5'末端。SL2反式剪接依赖于位于顺反子间区域(ICR)反式剪接位点上游约70个核苷酸处的富含U的元件(Ur),以及功能性的3'末端形成信号。在此,我们报告了一种新的基因长度RNA即Ur-RNA的存在,它起始于Ur元件的上游。Ur-RNA的表达依赖于3'末端的形成以及Ur元件的存在,但不需要反式剪接位点。Ur-RNA没有帽结构,并且Ur元件在5'或3'方向上位置的改变会改变Ur-RNA 5'末端的位置。我们提出,一种5'至3'外切核酸酶在多聚腺苷酸化位点切割后降解前体RNA,当它到达Ur元件时停止,推测这归因于一种结合蛋白。该蛋白的部分功能可由MS2外壳蛋白执行。在没有Ur元件的情况下,将外壳蛋白募集到ICR会导致一种与Ur-RNA等效的RNA积累,并恢复反式剪接。然而,仅使用SL1。因此,外壳蛋白足以阻断外切核酸酶,从而允许形成反式剪接的底物,但它缺乏募集SL2 snRNP的能力。我们的结果还表明,MS2外壳蛋白可作为体内外切核酸酶的阻断剂,这在mRNA稳定性研究中应具有实用性。