Pillai Ramesh S, Grimmler Matthias, Meister Gunter, Will Cindy L, Lührmann Reinhard, Fischer Utz, Schümperli Daniel
Institute of Cell Biology, University of Bern, 3012 Bern, Switzerland.
Genes Dev. 2003 Sep 15;17(18):2321-33. doi: 10.1101/gad.274403.
A set of seven Sm proteins assemble on the Sm-binding site of spliceosomal U snRNAs to form the ring-shaped Sm core. The U7 snRNP involved in histone RNA 3' processing contains a structurally similar but biochemically unique Sm core in which two of these proteins, Sm D1 and D2, are replaced by Lsm10 and by another as yet unknown component. Here we characterize this factor, termed Lsm11, as a novel Sm-like protein with apparently two distinct functions. In vitro studies suggest that its long N-terminal part mediates an important step in histone mRNA 3'-end cleavage, most likely by recruiting a zinc finger protein previously identified as a processing factor. In contrast, the C-terminal part, which comprises two Sm motifs interrupted by an unusually long spacer, is sufficient to assemble with U7, but not U1, snRNA. Assembly of this U7-specific Sm core depends on the noncanonical Sm-binding site of U7 snRNA. Moreover, it is facilitated by a specialized SMN complex that contains Lsm10 and Lsm11 but lacks Sm D1/D2. Thus, the U7-specific Lsm11 protein not only specifies the assembly of the U7 Sm core but also fulfills an important role in U7 snRNP-mediated histone mRNA processing.
一组七种Sm蛋白在剪接体U snRNA的Sm结合位点上组装，形成环状Sm核心。参与组蛋白RNA 3'加工的U7 snRNP含有结构相似但生化特性独特的Sm核心，其中两种蛋白Sm D1和D2被Lsm10和另一种未知成分取代。在这里，我们将这种因子（称为Lsm11）鉴定为一种具有两种明显不同功能的新型Sm样蛋白。体外研究表明，其长的N端部分介导了组蛋白mRNA 3'末端切割的一个重要步骤，很可能是通过招募一种先前被鉴定为加工因子的锌指蛋白来实现的。相比之下，C端部分由两个被异常长的间隔区打断的Sm基序组成，足以与U7 snRNA组装，但不能与U1 snRNA组装。这种U7特异性Sm核心的组装取决于U7 snRNA的非规范Sm结合位点。此外，一种特殊的包含Lsm10和Lsm11但缺乏Sm D1/D2的SMN复合物促进了其组装。因此，U7特异性Lsm11蛋白不仅决定了U7 Sm核心的组装，而且在U7 snRNP介导的组蛋白mRNA加工中发挥重要作用。
