Minvielle-Sebastia L, Beyer K, Krecic A M, Hector R E, Swanson M S, Keller W
Department of Cell Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.
EMBO J. 1998 Dec 15;17(24):7454-68. doi: 10.1093/emboj/17.24.7454.
Endonucleolytic cleavage of pre-mRNAs is the first step during eukaryotic mRNA 3' end formation. It has been proposed that cleavage factors CF IA, CF IB and CF II are required for pre-mRNA 3' end cleavage in yeast. CF IB is composed of a single polypeptide, Nab4p/Hrp1p, which is related to the A/B group of metazoan heterogeneous nuclear ribonucleoproteins (hnRNPs) that function as antagonistic regulators of 5' splice site selection. Here, we provide evidence that Nab4p/Hrp1p is not required for pre-mRNA 3' end endonucleolytic cleavage. We show that CF IA and CF II devoid of Nab4p/Hrp1p are sufficient to cleave a variety of RNA substrates but that cleavage occurs at multiple sites. Addition of Nab4p/Hrp1p prevents these alternative cleavages in a concentration-dependent manner, suggesting an essential and conserved role for some hnRNPs in pre-mRNA cleavage site selection.
前体mRNA的核酸内切裂解是真核生物mRNA 3'端形成过程中的第一步。有人提出,裂解因子CF IA、CF IB和CF II是酵母前体mRNA 3'端裂解所必需的。CF IB由单一多肽Nab4p/Hrp1p组成,它与后生动物异质核糖核蛋白(hnRNP)的A/B组相关,后者作为5'剪接位点选择的拮抗调节因子发挥作用。在这里,我们提供证据表明,前体mRNA 3'端核酸内切裂解不需要Nab4p/Hrp1p。我们发现,不含Nab4p/Hrp1p的CF IA和CF II足以裂解多种RNA底物,但裂解发生在多个位点。添加Nab4p/Hrp1p以浓度依赖的方式阻止这些替代裂解,这表明一些hnRNP在前体mRNA裂解位点选择中具有重要且保守的作用。