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

Abstract

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 and DMSMaPseq 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. Furthermore, 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.