University of Liverpool, School of Biological Sciences, Crown Street, Liverpool L69 7ZB, United Kingdom.
Mol Cell Biol. 2010 Jan;30(2):460-9. doi: 10.1128/MCB.00997-09. Epub 2009 Nov 9.
In eukaryotes, mRNA decay is generally initiated by the shortening of the poly(A) tail mediated by the major deadenylase complex Ccr4-Caf1-Not. The deadenylated transcript is then rapidly degraded, primarily via the decapping-dependent pathway. Here we report that in Aspergillus nidulans both the Caf1 and Ccr4 orthologues are functionally distinct deadenylases in vivo: Caf1 is required for the regulated degradation of specific transcripts, and Ccr4 is responsible for basal degradation. Intriguingly disruption of the Ccr4-Caf1-Not complex leads to deadenylation-independent decapping. Additionally, decapping is correlated with a novel transcript modification, addition of a CUCU sequence. A member of the nucleotidyltransferase superfamily, CutA, is required for this modification, and its disruption leads to a reduced rate of decapping and subsequent transcript degradation. We propose that 3' modification of adenylated mRNA, which is likely to represent a common eukaryotic process, primes the transcript for decapping and efficient degradation.
在真核生物中,mRNA 衰变通常是由主要的脱腺苷酸酶复合物 Ccr4-Caf1-Not 介导的 poly(A)尾巴缩短引发的。脱腺苷酸化的转录本随后会迅速降解,主要通过依赖脱帽的途径进行。在这里,我们报告在构巢曲霉中,Caf1 和 Ccr4 同源物在体内是功能不同的脱腺苷酸酶:Caf1 是特定转录本调控降解所必需的,而 Ccr4 负责基础降解。有趣的是,破坏 Ccr4-Caf1-Not 复合物会导致脱腺苷酸化非依赖性脱帽。此外,脱帽与一种新的转录本修饰,即添加 CUCU 序列相关。核苷转移酶超家族的一个成员 CutA 是这种修饰所必需的,其破坏会导致脱帽和随后的转录本降解速度降低。我们提出,对腺苷酸化 mRNA 的 3'修饰可能代表一种常见的真核生物过程,为脱帽和有效降解转录本做好准备。