Pannone B K, Xue D, Wolin S L
Departments of Cell Biology, Molecular Biophysics and Biochemistry and Howard Hughes Medical Institute, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06536, USA.
EMBO J. 1998 Dec 15;17(24):7442-53. doi: 10.1093/emboj/17.24.7442.
The first protein that binds to all newly synthesized RNA polymerase III transcripts is a highly conserved phosphoprotein known as the La autoantigen. Although binding by the yeast La protein Lhp1p to pre-tRNAs is required for the normal pathway of tRNA maturation, the role of the La protein in the biogenesis of other polymerase III transcripts has been unclear. We identified a mutation in a novel component of the U6 snRNP that causes yeast cells to require Lhp1p for growth. This protein, Lsm8p, is a member of a family of proteins, known as Sm-like proteins, that shares two conserved motifs with the core Sm proteins of the U1, U2, U4 and U5 snRNPs. The lsm8-1 cells have drastically reduced levels of the mature U6 snRNP, consistent with a defect in U6 snRNP assembly. In these cells, Lhp1p stabilizes newly synthesized U6 RNA, thus facilitating assembly of the RNA into the U6 snRNP. These results provide evidence that Lhp1p is a molecular chaperone for polymerase III-transcribed RNAs and implicate Lsm8p as a key component in the very early steps of U6 snRNP assembly.
首个与所有新合成的RNA聚合酶III转录本结合的蛋白质是一种高度保守的磷蛋白，即La自身抗原。尽管酵母La蛋白Lhp1p与前体tRNA的结合是tRNA成熟正常途径所必需的，但La蛋白在其他聚合酶III转录本生物合成中的作用尚不清楚。我们在U6 snRNP的一个新组分中鉴定出一个突变，该突变导致酵母细胞生长需要Lhp1p。这种蛋白质Lsm8p是一类被称为Sm样蛋白的蛋白质家族的成员，它与U1、U2、U4和U5 snRNPs的核心Sm蛋白共有两个保守基序。lsm8-1细胞中成熟U6 snRNP的水平大幅降低，这与U6 snRNP组装缺陷一致。在这些细胞中，Lhp1p稳定新合成的U6 RNA，从而促进RNA组装到U6 snRNP中。这些结果证明Lhp1p是聚合酶III转录RNA的分子伴侣，并表明Lsm8p是U6 snRNP组装非常早期步骤中的关键组分。
