Table of Contents
Research Articles
Toxicity of C9orf72-associated dipeptide repeat peptides is modified by commonly used protein tagsProtein tags affect the toxicity of C9orf72-associated dipeptide repeat proteins and therefore should be avoided in preclinical models of C9orf72 ALS and FTD.
MiR-93-5p inhibits retinal neurons apoptosis by regulating PDCD4 in acute ocular hypertension modelIt is found that miR-93-5p decreases retinal neuron apoptosis through suppressing PDCD4 in acute ocular hypertension model, which indicates miR-93-5p as a therapeutic target of glaucoma.
PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinasePIP4K is a lipid kinase implicated in tumour growth, immune function, and metabolic regulation. This study shows that PIP4K regulates PI3P levels and autophagy, thereby controlling cell size in Drosophila salivary glands.
Hypoxia controls expression of kidney-pathogenic MUC1 variantsHypoxia or pharmacological treatment with novel HIF stabilizers promotes the expression of MUC1 genetic variants that predispose to the development of chronic kidney disease in renal tubular cells.
Time-resolved proteomic analyses of senescence highlight metabolic rewiring of mitochondriaTime-resolved proteomic analyses of senescent fibroblasts reveal that nearly 40% of the analyzed mitochondrial proteome have changed upon induction of senescence. Our study highlights the rewiring of mitochondrial metabolism as a central feature among all changes in mitochondrial pathways of senescent cells.
Distant sequence regions of JBP1 contribute to J-DNA bindingStructural modeling and mutagenesis reveal that the N-terminus and DNA-binding domain of JBP1 recognize base-J, enabling replication of this epigenetic marker by JBP1’s thymidine hydroxylase domain.
Clec12a inhibits MSU-induced immune activation through lipid raft expulsionC type lection receptor Clec12a inhibits MSU induced Dendritic cell activation via its transmembrane domain rather than intracellular ITIM.
Differential roles of CTP synthetases CTPS1 and CTPS2 in cell proliferationThe CTP nucleotide is essential for cell proliferation. This study explores the respective contributions of CTP synthetases 1 and 2 in cell proliferation. Compared with CTPS2, CTPS1 is the main contributor in association with its higher enzymatic activity.
The linker histone H1–BRCA1 axis is a crucial mediator of replication fork stabilityThe replication-dependent histones H1 interact with BRCA1 upon replication stress. Cells deficient for H1 fail to recruit BRCA1 to stalled replication forks and undergo fork resection and collapse.
Peripheral immune system modulates Purkinje cell degeneration in Niemann–Pick disease type C1We demonstrate that peripheral immune cells are involved in the cerebral neuronal degeneration in Niemann–Pick disease type C1. Our work can contribute to a novel therapeutic strategy that can potentially be combined with the ongoing lipid reduction therapeutic efforts.
MAP4K4 regulates forces at cell–cell and cell–matrix adhesions to promote collective cell migrationUsing A431 carcinoma cells, the study shows that MAP4K4 coordinates cluster migration by regulating forces and stability of focal adhesions and adherens junctions, promoting cytoskeleton rearrangements.
The mRNA decapping machinery targets LBD3/ASL9 to mediate apical hook and lateral root developmentThis study identifies LBD3/ASL9 as targets of mRNA decay machinery, and ASL9 contributes to apical hook and lateral root development, possibly through interfering with cytokinin/auxin responses.
AR activates YAP/TAZ differentially in prostate cancerWe show YAP and TAZ are differentially activated upon androgen stimulation. Through genetic targeting of YAP, we show that YAP drives the ability for anchorage independent growth and find that YAP/TAZ is not essential for AR signalling.
β-Catenin regulates endocardial cushion growth by suppressing p21This work demonstrates that β-catenin–mediated suppression of p21 is essential for endocardial cushion formation, suggesting a potential role of β-catenin in the etiology of congenital heart defects.
The NSL complex is required for piRNA production from telomeric clustersGermline knockdown of the NSL complex leads to transposon derepression, particularly of telomeric transposons. NSL2 binds promoters of telomeric transposons and its depletion leads to alterations in the chromatin state of multiple telomeric piRNA clusters.
ACE2-EGFR-MAPK signaling contributes to SARS-CoV-2 infectionSARS-CoV-2 activates the conserved EGFR-RAS-MAPK pathway through a novel mechanism that involves an ACE2-EGFR cross talk and pharmacological inhibition of the MAPK pathway is able to reduce viral infection.
Structural insights into CED-3 activationThey report cryo-EM structures of CED-4 and three CED-4/CED-3 complexes with multiple oligomeric states. CARD–CARD interaction between CED-4 and CED-3 is essential for CED-3 activation and the newly reported dynamic organization of CED-4 regulates the onset of apoptosis.
Disulfide stabilization reveals conserved dynamic features between SARS-CoV-1 and SARS-CoV-2 spikesSARS-CoV-1 spike protein is stabilized with engineered disulfide bonds, and cryo-EM imaging of these stabilized S-trimers reveals rare spike conformations.
Characterizing control of memory CD8 T cell differentiation by BTB-ZF transcription factor Zbtb20This work characterizes the transcriptional and epigenetic control of memory CD8 T cell differentiation by the BTB-ZF family transcription factor Zbtb20 using single cell RNA and ATAC sequencing and identifies direct genomic targets of Zbtb20 using CUT&RUN.
Differential roles of FOXC2 in the trabecular meshwork and Schlemm’s canal in glaucomatous pathologyFOXC2 is required in the Schlemm’s canal endothelium and neural crest-derived trabecular meshwork cells for the morphogenesis and maintenance of Schlemm’s canal.
B-cell targeting with anti-CD38 daratumumab: implications for differentiation and memory responsesDaratumumab is an anti-CD38–targeting antibody that depletes plasma cells. This study shows that daratumumab also disturbs humoral immune responses beyond depletion only and may be used as therapeutic in B cell–mediated autoimmune diseases.
Transcriptome-wide RNA binding analysis of C9orf72 poly(PR) dipeptidesC9orf72 poly(PR) binds to 558 RNAs in human cells, and the sequence GAAGA is enriched at its binding sites. Poly(PR) has nanomolar affinity for GAAGA RNA, and this RNA induces poly(PR) phase separation.
The pyruvate dehydrogenase complex regulates mitophagic trafficking and protein phosphorylationMutations in the PDC affect the phosphorylation and mitophagic trafficking of matrix proteins, through the novel regulation of associated kinases and a phosphatase. We suggest that this occurs by the direct allosteric regulation of the phosphatase and kinases by the PDC.
A SAM-key domain required for enzymatic activity of the Fun30 nucleosome remodelerBiochemical data suggest that the SAM-key domain of the budding yeast remodeler Fun30 is required for its nucleosome remodeling activity by regulating the catalytic ATPase.
Exploring the impact of dexamethasone on gene regulation in myeloma cellsThe study uncovers epigenomic changes associated with dexamethasone response heterogeneity in myeloma cells, revealing rewired promoter–enhancer interactions and DNA loop stabilization.
Methods
A network embedding approach to identify active modules in biological interaction networksThis study proposes the AMINE method as a flexible and efficient approach to identify active modules from a data embedding combining gene expression and interaction data.
Reviews
Transducing compressive forces into cellular outputs in cancer and beyondThe review identifies signaling and cell biology processes selectively induced by mechanical compressive forces on normal or pathological tissues such as tumors for the development of novel treatments.
Resources
Comparative membrane proteomics reveals diverse cell regulators concentrated at the nuclear envelopeA cohort of low-abundance transmembrane proteins concentrated at the nuclear envelope has been identified, predicting diverse new functions for this membrane system.
