GraphProt: modeling binding preferences of RNA-binding proteins

We present GraphProt, a computational framework for learning sequence- and structure-binding preferences of RNA-binding proteins (RBPs) from high-throughput experimental data. We benchmark GraphProt, demonstrating that the modeled binding preferences conform to the literature, and showcase the biological relevance and two applications of GraphProt models. First, estimated binding affinities correlate with experimental measurements. Second, predicted Ago2 targets display higher levels of expression upon Ago2 knockdown, whereas control targets do not. Computational binding models, such as those provided by GraphProt, are essential for predicting RBP binding sites and affinities in all tissues. GraphProt is freely available at http://www.bioinf.uni-freiburg.de/Software/GraphProt

Publisher Correction: Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration.

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Max-Planck-Gesellschaft (Max Planck Society); doi: https://doi.org/10.13039/50110000418

Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration.

Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: Max-Planck-Gesellschaft (Max Planck Society); doi: https://doi.org/10.13039/501100004189Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery. TE transcripts bind to and activate the innate immune receptor melanoma differentiation-associated protein 5 (MDA5) that generates an inflammatory response that is necessary for HSCs to exit quiescence. HSCs that lack MDA5 exhibit an impaired inflammatory response after chemotherapy and retain their quiescence, with consequent better long-term repopulation capacity. We show that the overexpression of ERV and LINE superfamily TE copies in wild-type HSCs, but not in Mda5-/- HSCs, results in their cycling. By contrast, after knockdown of LINE1 family copies, HSCs retain their quiescence. Our results show that TE transcripts act as ligands that activate MDA5 during haematopoietic regeneration, thereby enabling HSCs to mount an inflammatory response necessary for their exit from quiescence

Peakachu peaks of human uvCLAP datasets.

Peaks called for human uvCLAP (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE85155) data using PEAKachu (https://github.com/tbischler/PEAKachu)