ABSTRACT

One important task of eukaryotic cells is to translate only mRNAs that were correctly processed to prevent the production of truncated proteins, found in neurodegenerative diseases and cancer. Nuclear quality control of splicing requires the SR-like proteins Gbp2 and Hrb1 in S. cerevisiae, where they promote the degradation of faulty pre-mRNAs. Here we show that Gbp2 and Hrb1 also function in nonsense mediated decay (NMD) of spliced premature termination codon (PTC)-containing mRNAs. Our data support a model in which they are in a complex with the Upf-proteins and help to transmit the Upf1-mediated PTC recognition to the transcripts ends. Most importantly they appear to promote translation repression of spliced transcripts that contain a PTC and to finally facilitate degradation of the RNA, presumably by supporting the recruitment of the degradation factors. Therefore, they seem to control mRNA quality beyond the nuclear border and may thus be global surveillance factors. Identification of SR-proteins as general cellular surveillance factors in yeast will help to understand the complex human system in which many diseases with defects in SR-proteins or NMD are known, but the proteins were not yet recognized as general RNA surveillance factors.

摘要

真核细胞的一项重要任务是仅翻译经过正确加工的 mRNA，以防止在神经退行性疾病和癌症中发现截短蛋白质的产生。剪接的核质量控制需要酿酒酵母中的 SR 样蛋白 Gbp2 和 Hrb1，它们促进有缺陷的前 mRNA 的降解。在这里，我们显示 Gbp2 和 Hrb1 在含有 PTC 的剪接提前终止密码子 (PTC) 的无意义介导的衰变 (NMD) 中也起作用。我们的数据支持一个模型，其中它们与 Upf 蛋白形成复合物，并有助于将 Upf1 介导的 PTC 识别传递到转录物末端。最重要的是，它们似乎促进了含有 PTC 的剪接转录本的翻译抑制，并最终促进了 RNA 的降解，可能是通过支持降解因子的募集。因此，它们似乎控制核边界之外的 mRNA 质量，因此可能是全球监测因素。