Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1.

The Drosophila behaviour/human splicing (DBHS) proteins are a family of RNA/DNA binding cofactors liable for a range of cellular processes. DBHS proteins include the non-POU domain-containing octamer-binding protein (NONO) and paraspeckle protein component 1 (PSPC1), proteins capable of forming combinatorial dimers. Here, we describe the crystal structures of the human NONO and PSPC1 homodimers, representing uncharacterized DBHS dimerization states. The structures reveal a set of conserved contacts and structural plasticity within the dimerization interface that provide a rationale for dimer selectivity between DBHS paralogues. In addition, solution X-ray scattering and accompanying biochemical experiments describe a mechanism of cooperative RNA recognition by the NONO homodimer. Nucleic acid binding is reliant on RRM1, and appears to be affected by the orientation of RRM1, influenced by a newly identified 'β-clasp' structure. Our structures shed light on the molecular determinants for DBHS homo- and heterodimerization and provide a basis for understanding how DBHS proteins cooperatively recognize a broad spectrum of RNA targets. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

Citation

Gavin J Knott, Yee Seng Chong, Daniel M Passon, Xue-Hai Liang, Evelyne Deplazes, Maria R Conte, Andrew C Marshall, Mihwa Lee, Archa H Fox, Charles S Bond. Structural basis of dimerization and nucleic acid binding of human DBHS proteins NONO and PSPC1. Nucleic acids research. 2022 Jan 11;50(1):522-535

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PMID: 34904671

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