Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy.

Detailed knowledge of the molecular biology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial for understanding of viral replication, host responses, and disease progression. Here, we report gene expression profiles of three SARS-CoV- and SARS-CoV-2-infected human cell lines. SARS-CoV-2 elicited an approximately two-fold higher stimulation of the innate immune response compared to SARS-CoV in the human epithelial cell line Calu-3, including induction of miRNA-155. Single-cell RNA sequencing of infected cells showed that genes induced by virus infections were broadly upregulated, whereas interferon beta/lambda genes, a pro-inflammatory cytokines such as IL-6, were expressed only in small subsets of infected cells. Temporal analysis suggested that transcriptional activities of interferon regulatory factors precede those of nuclear factor κB. Lastly, we identified heat shock protein 90 (HSP90) as a protein relevant for the infection. Inhibition of the HSP90 activity resulted in a reduction of viral replication and pro-inflammatory cytokine expression in primary human airway epithelial cells.

Spatiotemporal m(i)RNA Architecture and 3' UTR Regulation in the C. elegans Germline.

In animal germlines, regulation of cell proliferation and differentiation is particularly important but poorly understood. Here, using a cryo-cut approach, we mapped RNA expression along the Caenorhabditis elegans germline and, using mutants, dissected gene regulatory mechanisms that control spatiotemporal expression. We detected, at near single-cell resolution, >10,000 mRNAs, >300 miRNAs, and numerous unannotated miRNAs. Most RNAs were organized in distinct spatial patterns. Germline-specific miRNAs and their targets were co-localized. Moreover, we observed differential 3' UTR isoform usage for hundreds of mRNAs. In tumorous gld-2 gld-1 mutants, gene expression was strongly perturbed. In particular, differential 3' UTR usage was significantly impaired. We propose that PIE-1, a transcriptional repressor, functions to maintain spatial gene expression. Our data also suggest that cpsf-4 and fipp-1 control differential 3' UTR usage for hundreds of genes. Finally, we constructed a "virtual gonad" enabling "virtual in situ hybridizations" and access to all data (https://shiny.mdc-berlin.de/spacegerm/).