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Conserved Structure Modules within the IncRNA SChLAP1 Mediate Protein Recognition Implicated in Aggressive Prostate Cancer

View ORCID ProfileEmily J. McFadden, View ORCID ProfileJames P. Falese, View ORCID ProfileAmanda E. Hargrove
doi: https://doi.org/10.1101/2021.10.21.465303
Emily J. McFadden
1Yale School of Medicine, Department of Molecular Biophysics and Biochemistry, New Haven, Connecticut, USA
2Duke University School of Medicine, Department of Biochemistry, Durham, North Carolina, USA
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James P. Falese
2Duke University School of Medicine, Department of Biochemistry, Durham, North Carolina, USA
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Amanda E. Hargrove
2Duke University School of Medicine, Department of Biochemistry, Durham, North Carolina, USA
3Duke University, Department of Chemistry, Durham, North Carolina, USA
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  • For correspondence: amanda.hargrove@duke.edu
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Abstract

The lncRNA Second Chromosome Locus Associated with Prostate 1 (SChLAP1) was previously identified as a predictive biomarker and driver of aggressive prostate cancer. Recent work suggests that SChLAP1 may bind the SWI/SNF chromatin remodeling complex to promote prostate cancer metastasis, though the exact role of SWI/SNF recognition is debated. To date, there are no detailed biochemical studies of apo SChLAP1 or the SChLAP1:SWI/SNF complex. Herein, we report the first secondary structure model of SChLAP1 utilizing SHAPE-MaP both in vitro and in cellulo. Comparison of the in vitro and in cellulo data via ΔSHAPE identified putative protein binding sites within SChLAP1, specifically to evolutionarily conserved exons of the transcript. We also demonstrate that global SChLAP1 secondary structure is sensitive to both purification method and magnesium concentration. Further, we identified a 3’-fragment of SChLAP1 (SChLAP1Frag) that harbors multiple potential protein binding sites and presents a robustly folded secondary structure, supporting a functional role for this region. This work lays the foundation for future efforts in selective targeting and disruption of the SChLAP1:protein interface and the development of new therapeutic avenues in prostate cancer treatment.

Competing Interest Statement

The authors have declared no competing interest.

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  • Acknowledgements updated.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted October 22, 2021.
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Conserved Structure Modules within the IncRNA SChLAP1 Mediate Protein Recognition Implicated in Aggressive Prostate Cancer
Emily J. McFadden, James P. Falese, Amanda E. Hargrove
bioRxiv 2021.10.21.465303; doi: https://doi.org/10.1101/2021.10.21.465303
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Conserved Structure Modules within the IncRNA SChLAP1 Mediate Protein Recognition Implicated in Aggressive Prostate Cancer
Emily J. McFadden, James P. Falese, Amanda E. Hargrove
bioRxiv 2021.10.21.465303; doi: https://doi.org/10.1101/2021.10.21.465303

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