Structural and Mechanistic Insights into Poly(uridine) Tract Recognition by the hnRNP聽C RNA Recognition Motif

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• 作者：Zuzana Cienikov谩 ; Fred F. Damberger ; Jonathan Hall ; Fr茅d茅ric H.-T. Allain ; Christophe Maris
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：October 15, 2014
• 年：2014
• 卷：136
• 期：41
• 页码：14536-14544
• 全文大小：499K
• ISSN：1520-5126

文摘

HnRNP C is a ubiquitous RNA regulatory factor and the principal constituent of the nuclear hnRNP聽core particle. The protein contains one amino-terminal RNA recognition motif (RRM) known to bind uridine (U)-rich sequences. This work provides a molecular and mechanistic understanding of this interaction. We solved the solution structures of the RRM in complex with poly(U) oligomers of five and seven nucleotides. The five binding pockets of RRM recognize uridines with an unusual 5鈥?to-3鈥?gradient of base selectivity. The target recognition is therefore strongly sensitive to base clustering, explaining the preference for contiguous uridine tracts. Using a novel approach integrating the structurally derived recognition consensus of the RRM with a thermodynamic description of its multi-register binding, we modeled the saturation of cellular uridine tracts by this protein. The binding pattern is remarkably consistent with the experimentally observed transcriptome-wide cross-link distribution of the full-length hnRNP聽C on short uridine tracts. This result re-establishes the RRM as the primary RNA-binding domain of the hnRNP聽C tetramer and provides a proof of concept for interpreting high-throughput interaction data using structural approaches.