NLS-binding deficient Kapβ2 reduces neurotoxicity via selective interaction with C9orf72-ALS/FTD dipeptide repeats.

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity.

Cryo-EM analysis of Pseudomonas phage Pa193 structural components.

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193.

Integrative structural analysis of Pseudomonas phage DEV reveals a genome ejection motor.

DEV is an obligatory lytic Pseudomonas phage of the N4-like genus, recently reclassified as Schitoviridae. The DEV genome encodes 91 ORFs, including a 3398 amino acid virion-associated RNA polymerase (vRNAP). Here, we describe the complete architecture of DEV, determined using a combination of cryo-electron microscopy localized reconstruction, biochemical methods, and genetic knockouts.

Non-redundant roles for the human mRNA decapping cofactor paralogs DCP1a and DCP1b.

Eukaryotic gene expression is regulated at the transcriptional and post-transcriptional levels, with disruption of regulation contributing significantly to human diseases. The 5' m7G mRNA cap is a central node in post-transcriptional regulation, participating in both mRNA stabilization and translation efficiency. In mammals, DCP1a and DCP1b are paralogous cofactor proteins of the mRNA cap hydrolase DCP2.

Engineered NLS-chimera downregulates expression of aggregation-prone endogenous FUS.

Importin β-superfamily nuclear import receptors (NIRs) mitigate mislocalization and aggregation of RNA-binding proteins (RBPs), like FUS and TDP-43, which are implicated in neurodegenerative diseases. NIRs potently disaggregate RBPs by recognizing their nuclear localization signal (NLS). However, disease-causing mutations in NLS compromise NIR binding and activity.