新生U1小核RNA 5'端保守的AU二核苷酸经过优化，以利于与核帽结合复合物相互作用。

The conserved AU dinucleotide at the 5' end of nascent U1 snRNA is optimized for the interaction with nuclear cap-binding-complex.

作者信息

Yeh Chung-Shu, Chang Shang-Lin, Chen Jui-Hui, Wang Hsuan-Kai, Chou Yue-Chang, Wang Chun-Hsiung, Huang Shih-Hsin, Larson Amy, Pleiss Jeffrey A, Chang Wei-Hau, Chang Tien-Hsien

机构信息

Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan.

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

出版信息

Nucleic Acids Res. 2017 Sep 19;45(16):9679-9693. doi: 10.1093/nar/gkx608.

Splicing is initiated by a productive interaction between the pre-mRNA and the U1 snRNP, in which a short RNA duplex is established between the 5' splice site of a pre-mRNA and the 5' end of the U1 snRNA. A long-standing puzzle has been why the AU dincucleotide at the 5'-end of the U1 snRNA is highly conserved, despite the absence of an apparent role in the formation of the duplex. To explore this conundrum, we varied this AU dinucleotide into all possible permutations and analyzed the resulting molecular consequences. This led to the unexpected findings that the AU dinucleotide dictates the optimal binding of cap-binding complex (CBC) to the 5' end of the nascent U1 snRNA, which ultimately influences the utilization of U1 snRNP in splicing. Our data also provide a structural interpretation as to why the AU dinucleotide is conserved during evolution.

剪接由前体mRNA与U1 snRNP之间的有效相互作用启动，其中在前体mRNA的5'剪接位点与U1 snRNA的5'末端之间形成短RNA双链体。一个长期存在的谜题是，尽管U1 snRNA 5'末端的AU二核苷酸在双链体形成中没有明显作用，但它为何高度保守。为了探究这个难题，我们将这个AU二核苷酸改变为所有可能的排列，并分析了由此产生的分子后果。这导致了意想不到的发现，即AU二核苷酸决定了帽结合复合物（CBC）与新生U1 snRNA 5'末端的最佳结合，这最终影响了U1 snRNP在剪接中的利用。我们的数据还为AU二核苷酸在进化过程中保守的原因提供了结构解释。