U1 snRNA 可在剪接抑制过程中与聚嘧啶 tract 结合蛋白直接相互作用。
U1 snRNA directly interacts with polypyrimidine tract-binding protein during splicing repression.
机构信息
Howard Hughes Medical Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA.
出版信息
Mol Cell. 2011 Mar 4;41(5):579-88. doi: 10.1016/j.molcel.2011.02.012.
Abstract
Splicing of the c-src N1 exon is repressed by the polypyrimidine tract-binding protein (PTB or PTBP1). During exon repression, the U1 snRNP binds properly to the N1 exon 5' splice site but is made inactive by the presence of PTB. Examining the patterns of nuclease protection at this 5' splice site, we find that the interaction of U1 is altered by the adjacent PTB. Interestingly, UV crosslinking identifies a direct contact between the pre-mRNA-bound PTB and the U1 snRNA. EMSA, ITC, and NMR studies show that PTB RRMs 1 and 2 bind the pyrimidine-rich internal loop of U1 snRNA stem loop 4. The PTB/U1 interaction prevents further assembly of the U1 snRNP with spliceosomal components downstream. This precise interaction between a splicing regulator and an snRNA component of the spliceosome points to a range of different mechanisms for splicing regulation.
摘要
c-src N1 外显子的剪接受多嘧啶 tract 结合蛋白 (PTB 或 PTBP1) 的抑制。在外显子抑制过程中，U1 snRNP 正确地结合到 N1 外显子 5' 剪接位点，但由于 PTB 的存在而失活。研究这个 5' 剪接位点的核酸酶保护模式，我们发现 U1 的相互作用被相邻的 PTB 改变。有趣的是，UV 交联鉴定了 pre-mRNA 结合的 PTB 和 U1 snRNA 之间的直接接触。EMSA、ITC 和 NMR 研究表明，PTB RRMs1 和 2 结合 U1 snRNA 茎环 4 中富含嘧啶的内环。PTB/U1 相互作用阻止 U1 snRNP 与剪接体下游的剪接体成分进一步组装。这种剪接调节剂和剪接体中 snRNA 成分之间的精确相互作用指出了多种不同的剪接调节机制。
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