Lotan Rona, Goler-Baron Vicky, Duek Lea, Haimovich Gal, Choder Mordechai
Department of Molecular Microbiology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa 31096, Israel.
J Cell Biol. 2007 Sep 24;178(7):1133-43. doi: 10.1083/jcb.200701165. Epub 2007 Sep 17.
The steady-state level of mRNAs is determined by the balance between their synthesis by RNA polymerase II (Pol II) and their decay. In the cytoplasm, mRNAs are degraded by two major pathways; one requires decapping and 5' to 3' exonuclease activity and the other involves 3' to 5' degradation. Rpb7p is a Pol II subunit that shuttles between the nucleus and the cytoplasm. Here, we show that Rpb7p is involved in the two mRNA decay pathways and possibly couples them. Rpb7p stimulates the deadenylation stage required for execution of both pathways. Additionally, Rpb7p is both an active component of the P bodies, where decapping and 5' to 3' degradation occur, and is capable of affecting the P bodies function. Moreover, Rpb7p interacts with the decapping regulator Pat1p in a manner important for the mRNA decay machinery. Rpb7p is also involved in the second pathway, as it stimulates 3' to 5' degradation. Our genetic analyses suggest that Rpb7p plays two distinct roles in mRNA decay, which can both be uncoupled from Rpb7p's role in transcription. Thus, Rpb7p plays pivotal roles in determining mRNA levels.
信使核糖核酸(mRNA)的稳态水平由RNA聚合酶II(Pol II)合成与降解之间的平衡所决定。在细胞质中,mRNA通过两条主要途径降解;一条途径需要去帽和5'至3'核酸外切酶活性,另一条途径涉及3'至5'降解。Rpb7p是一种穿梭于细胞核与细胞质之间的Pol II亚基。在此,我们表明Rpb7p参与了这两条mRNA降解途径,并可能将它们联系起来。Rpb7p刺激了两条途径执行所需的去腺苷酸化阶段。此外,Rpb7p既是P小体(发生去帽和5'至3'降解的场所)的活性成分,又能够影响P小体的功能。而且,Rpb7p以对mRNA降解机制很重要的方式与去帽调节因子Pat1p相互作用。Rpb7p还参与第二条途径,因为它刺激3'至5'降解。我们的遗传学分析表明,Rpb7p在mRNA降解中发挥两个不同的作用,这两个作用都可以与Rpb7p在转录中的作用解偶联。因此,Rpb7p在决定mRNA水平方面发挥着关键作用。