Segal Scott P, Dunckley Travis, Parker Roy
Department of Molecular Cellular Biology and Howard Hughes Medical Institute, University of Arizona, 1007 E. Lowell St., Tucson, AZ 85721, USA.
Mol Cell Biol. 2006 Jul;26(13):5120-30. doi: 10.1128/MCB.01913-05.
The relationship between translation and mRNA turnover is critical to the regulation of gene expression. One major pathway for mRNA turnover occurs by deadenylation, which leads to decapping and subsequent 5'-to-3' degradation of the body of the mRNA. Prior to mRNA decapping, a transcript exits translation and enters P bodies to become a potential decapping substrate. To understand the transition from translation to decapping, it is important to identify the factors involved in this process. In this work, we identify Sbp1p (formerly known as Ssb1p), an abundant RNA binding protein, as a high-copy-number suppressor of a conditional allele in the decapping enzyme. Sbp1p overexpression restores normal decay rates in decapping-defective strains and increases P-body size and number. In addition, Sbp1p promotes translational repression of mRNA during glucose deprivation. Moreover, P-body formation is reduced in strains lacking Sbp1p. Sbp1p acts in conjunction with Dhh1p, as it is required for translational repression and P-body formation in pat1Delta strains under these conditions. These results identify Sbp1p as a new protein that functions in the transition of mRNAs from translation to an mRNP complex destined for decapping.
翻译与mRNA周转之间的关系对于基因表达的调控至关重要。mRNA周转的一个主要途径是通过去腺苷酸化发生的,这会导致脱帽以及随后mRNA主体从5'到3'的降解。在mRNA脱帽之前,转录本退出翻译并进入P小体,成为潜在的脱帽底物。为了理解从翻译到脱帽的转变,识别参与这一过程的因子很重要。在这项工作中,我们鉴定出Sbp1p(以前称为Ssb1p),一种丰富的RNA结合蛋白,作为脱帽酶中一个条件等位基因的高拷贝数抑制因子。Sbp1p的过表达恢复了脱帽缺陷菌株中的正常降解速率,并增加了P小体的大小和数量。此外,Sbp1p在葡萄糖剥夺期间促进mRNA的翻译抑制。而且,在缺乏Sbp1p的菌株中P小体形成减少。在这些条件下,Sbp1p与Dhh1p协同作用,因为它是patlDelta菌株中翻译抑制和P小体形成所必需的。这些结果鉴定出Sbp1p是一种在mRNA从翻译转变为注定要脱帽的mRNP复合物过程中发挥作用的新蛋白。