Volume 28 Issue 2, February 2021

NUP98 is one of the most promiscuous fusion partners involved in leukemogenic chromosomal translocations, but the myriad of partners has long obfuscated the mechanism by which these fusion proteins drive leukemia. A new mass spectrometry–based approach has produced clues that suggest an entirely new model of leukemogenesis.

Resolving RNA polymerase structures at the atomic level has revolutionized our understanding of transcription. Three articles now published in Nature Structural & Molecular Biology and Nature Communications decipher unique properties of human RNA polymerase III and propose built-in modules within the enzyme that mediate transcriptional activation, repression and antirepression.

The SARS-CoV-2 spike ectodomain is destabilized by cold temperature storage, an effect that can be reversed by incubation at 37 °C or by stabilizing its conformation in the ‘down’ state.

Cytoplasmic aggregates of TDP-43 sequester specific miRNAs and subsets of proteins, causing dysregulation of mitochondrial proteins and a global mitochondrial imbalance that augments oxidative stress and may promote ALS initiation and progression.

Biochemical and biophysical analyses of eye lenses from mouse strains that develop cataract due to mutations in α-, β-, or γ-crystallin proteins reveal that the mutant protein levels are largely reduced, but other crystallin proteins, including α-crystallins, precipitate.

Acute loss of CTCF disproportionately affects the transcription of genes that display promoter-proximal CTCF binding and are dependent on long-distance enhancers.

Cryo-EM structures of fungal Sec61–Sec62–Sec63 complexes show how Sec63 and Sec62 work together in a hierarchical manner to activate the Sec61 channel for protein translocation into the endoplasmic reticulum.

Cryo-EM structures of nucleic acid–sensing Toll-like receptors in complex with their trafficking chaperone UNC93B1, a protein that mediates TLR compartmentalization important for self versus non-self discrimination, provide insights into their interaction.

The Ebola virus (EBOV) glycoprotein transmembrane domain interacts with membrane cholesterol. This interaction is required for viral fusion and cell entry and may explain why statins suppress EBOV infection.

A mass spectrometry–based approach is used to investigate the mechanisms by which different NUP98 fusion proteins cause leukemia, revealing that the fusion proteins share common interactors and alter the composition of nuclear condensates.

Engineered soluble trimeric ACE2 constructs with intact enzymatic activity and high affinity to SARS-CoV-2 spike are shown to inhibit viral infection in cellular assays.

Cryo-EM structures of human Pol III in both apo- and elongating states reveal metazoan-specific differences in the regulation of transcription termination and identify mutations relevant to human disease.

High-resolution cryo-EM structures of human RNA Pol III in both apo and elongating states provide insights into an autoinhibitory mechanism controlling the transition to transcription elongation unique to the mammalian holoenzyme.