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Title: Noncanonical registers and base pairs in human 5′ splice-site selection
Authors: Tan, Jiazi
Ho, Jessie Jia Xin
Zhong, Zhensheng
Luo, Shufang
Chen, Gang
Roca, Xavier
Keywords: RNA
DRNTU::Science::Biological sciences
Noncanonical Registers
Issue Date: 2016
Source: Tan, J., Ho, J. J. X., Zhong, Z., Luo, S., Chen, G., & Roca, X. (2016). Noncanonical registers and base pairs in human 5′ splice-site selection. Nucleic Acids Research, 44(8), 3908-3921. doi:10.1093/nar/gkw163
Series/Report no.: Nucleic Acids Research
Abstract: Accurate recognition of splice sites is essential for pre-messenger RNA splicing. Mammalian 5′ splice sites are mainly recognized by canonical base-pairing to the 5′ end of U1 small nuclear RNA, yet we described multiple noncanonical base-pairing registers by shifting base-pair positions or allowing one-nucleotide bulges. By systematic mutational and suppressor U1 analyses, we prove three registers involving asymmetric loops and show that two-nucleotide bulges but not longer can form in this context. Importantly, we established that a noncanonical uridine-pseudouridine interaction in the 5′ splice site/U1 helix contributes to the recognition of certain 5′ splice sites. Thermal melting experiments support the formation of noncanonical registers and uridine-pseudouridine interactions. Overall, we experimentally validated or discarded the majority of predicted noncanonical registers, to derive a list of 5′ splice sites using such alternative mechanisms that is much different from the original. This study allows not only the mechanistic understanding of the recognition of a wide diversity of mammalian 5′ splice sites, but also the future development of better splice-site scoring methods that reliably predict the effects of disease-causing mutations at these sequences.
ISSN: 0305-1048
Rights: © 2016 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact
Fulltext Permission: open
Fulltext Availability: With Fulltext
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