“QUADRatlas: the RNA G-Quadruplex and RG4-binding proteins database” скачать в хорошем качестве

“QUADRatlas: the RNA G-Quadruplex and RG4-binding proteins database”

“QUADRatlas: the RNA G-Quadruplex and RG4-binding proteins database” Sébastien Bourdon, CRCT, Toulouse RNA G-Quadruplexes (RG4s) are non-canonical structures that have been increasingly recognized as fundamental posttranscriptional regulators of gene expression (doi: 10.1016/j.tibs.2020.11.001). These elements are indeed able to affect cell physiology and pathology thanks to their dynamicity and wide array of interactors. In particular, they have been associated with the onset, progression, and therapy resistance in human cancers by us (doi: 10.1038/s41467-020-16168- x, 10.1084/jem.20210571) and several others. The current view is that RG4s are dynamic structures whose folding equilibrium and function are driven by RNA-binding proteins (doi: 10.1126/science.aaf5371, 10.1038/s41467-018-07224- 8). Our previous work uncovered a set of such proteins as potential RG4 interactors, suggesting that their regulatory network is far wider than initially expected. Being able to explore interactions with RNA-binding proteins (RBPs) and the role of RG4 in post-transcriptional control of gene expression is thus paramount to understanding how RG4s are regulated and exploiting them as potential therapeutic targets. To empower this analysis, we thus built QUADRatlas, a database including experimentally-derived (using publicly available RG4-seq datasets) and computationally predicted RG4s (using three tools and their consensus as a "golden standard") in the human transcriptome. We enriched these datasets with annotations describing the biological function and disease phenotype associations for RG4s, as obtained from the literature. Users of our database can thus explore RG4s in specific transcripts of their interest, obtaining details on their function and pathological potential. The database currently includes only human data, but we plan to expand it to the mouse and potentially other organisms. To this end, the underlying software is already able to accommodate multiple organisms seamlessly. Recognizing that the interaction of RG4s with RBPs is key to their function, we then mined known interactions of RG4s with such proteins, complementing them with the extensive dataset of ENCODE eCLIP assays. We thus provide binding sites for many RBPs and allow our users to intersect the RG4s with their potential regulators and effectors. We thus enable the formulation of novel hypotheses on RG4 regulation, function,