Genetics, Gene Therapy & Genetic Disease
Heterozygous loss of function of IQSEC2/Iqsec2 leads to increased activated Arf6 and severe neurocognitive seizure phenotype in femalesWe show that the loss of Iqsec2 function in mice recapitulates key aspects of the human phenotype, irrespective of the X-inactivation status of the gene between species. Our understanding of the traditional X-chromosome inheritance with heterozygous female sparing needs revisiting.
PRDM9 forms a trimer by interactions within the zinc finger arrayPRDM9 forms a trimer as a soluble protein and in complex with DNA mediated by the ZnF domain. Five ZnFs are already sufficient for multimerization and only one DNA molecule is complexed in the trimer.
CRISPR-induced double-strand breaks trigger recombination between homologous chromosome armsCRISPR–Cas9 enables recombination between homologous chromosome arms at predefined sites and also underscores the need for caution when applying CRISPR technologies in translational medicine.
The hypoxia-response pathway modulates RAS/MAPK–mediated cell fate decisions in Caenorhabditis elegansAtmospheric oxygen levels modulate the RAS/MAPK signaling pathway in the nematode Caenorhabditis elegans through a cross-talk between the DELTA/NOTCH and hypoxia signaling pathways. These mechanisms may permit the animals to adapt their development to changes in the environment.
The impact of poly-A microsatellite heterologies in meiotic recombinationMeiosis strongly influences the transmission and evolution of heterozygous poly-A repeats as measured experimentally in a large collection of single recombination products in a human hotspot.
Drug screening with human SMN2 reporter identifies SMN protein stabilizers to correct SMA pathologyThis study has established a versatile human SMN2 reporter line for drug screening and identified a novel strategy of targeting cysteine proteases for rescuing SMA pathological phenotypes.
PISD is a mitochondrial disease gene causing skeletal dysplasia, cataracts, and white matter changesThis work demonstrates that pathogenic variants in PISD cause mitochondrial disease and suggests a novel mechanistic link whereby impaired lipid content in the inner mitochondrial membrane alters the activity of inner mitochondrial membrane proteases.
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.
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.
An essential role for α4A-tubulin in platelet biogenesisAlpha4A-tubulin is the predominant α-tubulin isotype in platelets. Mutations in α4A-tubulin cause abnormal platelet biogenesis and marginal band formation in mice and in a patient, establishing an essential role of this tubulin isotype.