The Conserved AU Dinucleotide at the 5’ End of Nascent U1 snRNA is Optimized for the Interaction with Nuclear Cap-Binding-Complex

• Main Authors: Chung-Shu Yeh, 葉仲書
• Other Authors: Tien-Hsien Chang
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/8ks3e6

博士 === 國立陽明大學 === 生化暨分子生物研究所 === 105 === 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, I 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. My data also provide a structural interpretation as to why the AU dinucleotide is conserved during evolution.