Structural analysis of the lncRNA SChLAP1 reveals protein binding interfaces and a conformationally heterogenous retroviral insertion

The lncRNA Second Chromosome Locus Associated with Prostate 1 (SChLAP1) was previously identified as a predictive biomarker and potential 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 SChLAP1:protein complexes. Herein, we report the first secondary structure model of SChLAP1 using SHAPE-MaP in vitro, in cellulo, and ex cellulo (protein-free). Comparison of the ex cellulo and in cellulo data via ?SHAPE identified putative protein binding sites within SChLAP1. In addition, we identified primate conserved exons of SChLAP1 as well as regions that appear to have been incorporated through retroviral insertion. In particular, we characterized a complex structural landscape in a protein binding region at the 3'-end of SChLAP1 derived from a THE1B-type retroviral insertion, suggesting a role for an exapted RNA structure in SChLAP1:protein recognition and prostate cancer progression. This work lays the foundation for future efforts to selectively target and disrupt the SChLAP1:protein interface and to develop new therapeutic avenues in prostate cancer treatment. Overall design: DNA-seq of libraries derived from mock (DMSO) or SHAPE-probed SChLAP1 RNA. Biological duplicate obtained for in cellulo and ex cellulo samples, and unicate obtained of in vitro samples. DMS probing performed with ethanol control of in vitro SChLAP1 in biological unicate. Please note that the processed data generated from both DMSO and SHAPE samples is linked to the corresponding DMSO sample records.