Molecular Biology
FUS (fused in sarcoma) is a component of the cellular response to topoisomerase I–induced DNA breakage and transcriptional stressThis work shows that the ALS-associated protein FUS is a component of the cellular response to transcriptional stress induced by topoisomerase I–induced DNA breakage, thereby accumulating at sites of nucleolar rRNA synthesis.
Main constraints for RNAi induced by expressed long dsRNA in mouse cellsA systematic survey of dsRNA expression in mouse fibroblasts and embryonic stem cells shows main constraints for RNAi. RNAi activity depends on the initial Dicer cleavage of dsRNA, having implications for the evolution of mammalian RNAi functions.
MiR-146a wild-type 3′ sequence identity is dispensable for proper innate immune function in vivoMice engineered to express an allele of a mammalian microRNA in which the 3′ paring specificity of the mature miRNA is robustly altered are phenotypically indistinguishable from mice with the wild-type allele.
Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathyVamorolone is a first-in-class dissociative drug that selectively targets the glucocorticoid receptor to safely treat chronic inflammation and the mineralocorticoid receptor to treat cardiomyopathy, providing efficacy with improved safety in mouse models of Duchenne muscular dystrophy.
Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund–Thomson syndromeRECQL4, which is mutated in the Rothmund–Thomson syndrome characterized by premature aging and cancer susceptibility, is a microtubule-associated protein required for mitotic chromosome alignment.
Mitochondrial stress response triggered by defects in protein synthesis quality controlQuality control defects of mitochondrial nascent chain synthesis trigger a sequential stress response characterized by OMA1 activation and ribosome decay, determining mitochondrial form and function.
Folding–function relationship of the most common cystic fibrosis–causing CFTR conductance mutantsThe tight correlation between folding and function in cystic fibrosis patients with CFTR mutations of the altered-conductance CFTR class provides an attractive paradigm for characterizing mode of action of novel therapeutics.
Rab1b and ARF5 are novel RNA-binding proteins involved in FMDV IRES–driven RNA localizationIntegration of proteomic data with functional and imaging analysis revealed that Rab1b and ARF5, two ER-Golgi members, are RNA-binding proteins that colocalize with picornavirus IRES-RNA reporters in human cells.
Direct binding of Cdt2 to PCNA is important for targeting the CRL4Cdt2 E3 ligase activity to Cdt1The C-terminal end of Cdt2 contains a PIP box for binding to PCNA to promote CRL4Cdt2 function, creating a new paradigm where the substrate receptor and substrates bind to a common multivalent docking platform for ubiquitination.
Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with MEI4Mouse REC114 is essential for meiotic DNA double-strand break formation and forms a complex with IHO1. Its N-terminal region forms a Pleckstrin homology domain, while its C-terminal region is interacting with MEI4.