Molecular Biology
let-7 coordinates the transition to adulthood through a single primary and four secondary targetsAlthough miRNAs may act through regulation of numerous targets, this study shows that the Caenorhabditis elegans let-7 miRNA promotes the juvenile-to-adult transition through repression of LIN41 alone, thereby activating four LIN41 targets that function in pairs to execute distinct developmental functions.
Expanding the repertoire of glucocorticoid receptor target genes by engineering genomic response elementsThis study shows that addition of a single transcription factor binding site can be sufficient to convert a gene into a glucocorticoid receptor target.
The small and large ribosomal subunits depend on each other for stability and accumulationStopping 60S assembly blocks accumulation of 40S by post-assembly turnover, whereas inhibiting 40S assembly allows 60S assembly but results in fragmentation of 25S rRNA.
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.