Schwede Angela, Ellis Louise, Luther Julia, Carrington Mark, Stoecklin Georg, Clayton Christine
Zentrum für Molekulare Biologie der Universität Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.
Nucleic Acids Res. 2008 Jun;36(10):3374-88. doi: 10.1093/nar/gkn108. Epub 2008 Apr 27.
The eukaryotic Ccr4/Caf1/Not complex is involved in deadenylation of mRNAs. The Caf1 and Ccr4 subunits both potentially have deadenylating enzyme activity. We investigate here the roles of Ccr4 and Caf1 in deadenylation in two organisms that separated early in eukaryotic evolution: humans and trypanosomes. In Trypanosoma brucei, we found a complex containing CAF1, NOT1, NOT2 and NOT5, DHH1 and a possible homologue of Caf130; no homologue of Ccr4 was found. Trypanosome CAF1 has deadenylation activity, and is essential for cell survival. Depletion of trypanosome CAF1 delayed deadenylation and degradation of constitutively expressed mRNAs. Human cells have two isozymes of Caf1: simultaneous depletion of both inhibited degradation of an unstable reporter mRNA. In both species, depletion of Caf1 homologues inhibited deadenylation of bulk RNA and resulted in an increase in average poly(A) tail length.
真核生物的Ccr4/Caf1/Not复合物参与mRNA的去腺苷酸化过程。Caf1和Ccr4亚基都可能具有去腺苷酸化酶活性。我们在此研究Ccr4和Caf1在真核生物进化早期就已分化的两种生物——人类和锥虫——的去腺苷酸化过程中的作用。在布氏锥虫中，我们发现了一个包含CAF1、NOT1、NOT2和NOT5、DHH1以及Caf130可能同源物的复合物；未发现Ccr4的同源物。锥虫CAF1具有去腺苷酸化活性，且对细胞存活至关重要。布氏锥虫CAF1的缺失延迟了组成型表达mRNA的去腺苷酸化和降解。人类细胞有两种Caf1同工酶：同时缺失这两种同工酶会抑制不稳定报告mRNA的降解。在这两个物种中，Caf1同源物的缺失均抑制了总体RNA的去腺苷酸化，并导致平均多聚腺苷酸尾长度增加。
