The innate immune cGAS-STING pathway is activated by cytosolic double-stranded DNA (dsDNA), a ubiquitous danger signal, to produce interferon. However, STING activation must be tightly controlled because aberrant interferon production leads to debilitating interferonopathies. Here, we discover PELI2 as a crucial negative regulator of STING.
Genomic rearrangements, encompassing mutational changes in the genome such as insertions, deletions, or inversions, are essential for genetic diversity. We report that IS110 insertion sequences, a family of minimal and autonomous mobile genetic elements, express a structured non-coding RNA that binds specifically to their encoded recombinase.
Effective and precise mammalian transcriptome engineering technologies are needed to accelerate biological discovery. Here, we quantified the performance of over 127,000 CasRx guide RNAs and systematically evaluated seven machine learning models to build a guide efficiency prediction algorithm orthogonally validated across multiple human cell types.
Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) expression correlates with poor prognosis in many cancers. Here, using single-cell RNA-seq, we show that ENPP1 in both cancer and normal tissues drives primary breast tumor growth and metastasis by dampening extracellular cGAMP–STING-mediated antitumoral immunity.
Here, we developed a framework for mapping context-specific genetic interactions, enabling us to measure the plasticity of human genetic architecture upon environmental challenge for ∼250,000 interactions, using cell cycle interruption, genotoxic perturbation, and nutrient deprivation as archetypes.
Here we profiled antisense RNAs in the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one antisense RNA that drives cancer progression by upregulating the redox enzyme NADPH quinone dehydrogenase 1 (NQO1), and named it NQO1-AS.