Insight into the structural basis for dual nucleic acid - recognition by the Scaffold Attachment Factor B2 protein

Korn, S. M.; von Ehr, J.; Dhamotharan, K.; Tants, J.-N.; Abele, R.; Schlundt, A.

doi:10.1101/2022.12.28.522114

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bioRxiv · 10.1101/2022.12.28.522114

Insight into the structural basis for dual nucleic acid - recognition by the Scaffold Attachment Factor B2 protein

Korn, S. M.·von Ehr, J.·Dhamotharan, K.·Tants, J.-N.·Abele, R.·Schlundt, A.

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Abstract

The family of scaffold attachment factor B (SAFB) proteins comprises three members and was first identified as binders of the nuclear matrix/scaffold. Over the past two decades, SAFBs were shown to act in DNA repair, mRNA/(l)ncRNA processing, and as part of protein complexes with chromatin-modifying enzymes. SAFB proteins are approximately-100-kDa-sized dual nucleic acid-binding proteins with dedicated domains in an otherwise largely unstructured context, but whether and how they discriminate DNA- and RNA-binding has remained enigmatic. We here provide the SAFB2 DNA- and RNA-binding SAP and RRM domains in their functional boundaries and use solution NMR spectroscopy to ascribe DNA- and RNA-binding functions. We give insight into their target nucleic acid preferences and map the interfaces with respective nucleic acids on sparse data-derived SAP and RRM domain structures. Further, we provide evidence that the SAP domain exhibits intra-domain dynamics and a potential tendency to dimerise, which may expand its specifically targeted DNA sequence range. Our data provide a first molecular basis of and a starting point towards deciphering DNA- and RNA-binding functions of SAFB2 on the molecular level and serve a basis for understanding its localization to specific regions of chromatin and its involvement in the processing of specific RNA species.

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Korn, S. M., von Ehr, J., Dhamotharan, K., Tants, J.-N., Abele, R., Schlundt, A.. 2022-12-29. Insight into the structural basis for dual nucleic acid - recognition by the Scaffold Attachment Factor B2 protein. https://doi.org/10.1101/2022.12.28.522114

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