Brief Communications

Gao, Nardone et al. report the cryo-EM structure of human TXNL1 bound to the proteasome and reveal interactions required for the stress-induced degradation of TXNL1, an abundant protein that may regulate proteasomal activity.

Using cryo-electron microscopy and biochemical analysis, the authors reveal the mechanism of transcriptional inhibition by the noncoding RNA Alu and provide insights into relief of inhibition by the general transcription factor TFIIF.

The authors use cryo-electron microscopy to reveal two structural states of Ca²⁺-activated gelsolin bound to the actin filament, illuminating the mechanisms of filament severing and barbed end capping.

This study presents the cryo-electron microscopy structure of Fanzor2, showcasing its unique structural elements and nucleic acid interaction sites. A comparison to TnpB-related RNA-guided endonucleases highlights divergent evolutionary paths.

Here, using cryo-electron microscopy to study the structure of LRPPRC (leucine-rich pentatricopeptide repeat-containing protein) in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), mRNA and the mitoribosome, the authors show that LRPPRC facilitates mRNA handoff to the mitoribosome and regulates the expression of several mitochondrial genes.

This study reveals the mechanisms of NEAT1 lncRNA maturation and menRNA biogenesis and uncovers an RNA-centric, riboswitch-like mechanism where menRNA drives its own conformational isomerization that directs repeat CCA addition and rapid degradation.

Cryo-EM studies reveal that RYBP–PRC1 uses two distinct interfaces for binding unmodified and H2Aub1-modified nucleosomes. These binding modes enable the complex to generate H2Aub1 chromatin domains by a read–write mechanism.

The biogenesis and recycling of the ‘heart’ of the human spliceosome, the U5 small nuclear ribonucleoprotein (snRNP), requires CD2BP2 and TSSC4. Here the authors present cryo-electron microscopy structures that reveal how these protein chaperones orchestrate the ATP-independent (re)generation of the U5 snRNP.

Here the authors report the structure of the human 20S U5 snRNP, providing new insights into the assembly of the spliceosome building blocks.

Using deep mutational scanning, the authors uncover the functional consequence of missense mutations in ARID1B, a subunit of the SWI/SNF chromatin remodeling complex that is frequently mutated in human Coffin–Siris syndrome and in cancer.

Structures of complete extracellular receptor assemblies mediated by the pro-inflammatory cytokines IL-12 and IL-23 reveal key commonalities and diverse features, with only IL-12 juxtaposing receptor domains proximal to the cell membrane.

This study revealed the mechanism by which the E3 ligase Bre1 directs monoubiquitination of histone H2B at K123 by the E2 ubiquitin-conjugating enzyme Rad6. Comparison with other dimeric E3 ligases suggests a pivot-like mechanism in which one subunit ‘tunes’ the specificity for particular histone residues.

Here, the authors present droplet-based Paired-Tag, an improved method to concomitantly map histone modifications and gene expression at single-cell resolution. They functionally benchmark the method and demonstrate its advantages in mammalian cells and primary brain tissues.

Here, the authors demonstrate that the translation of the Drosophila transcript of insulin (dilp2) is regulated by methylation of N⁶-adenosine (m⁶A) in the 3′ UTR, at sites also conserved in mammals. In turn, this results in aberrant, diabetes-like functional phenotypes.

Here, the authors solve the cryogenic electron microscopy structure of a human primosome to shed light on the mechanism by which RNA–DNA primers are synthesized for the initiation of DNA replication and the structural basis of the primer length limitation.

Gabapentinoid drugs are widely used for pain, epilepsy and mental disorders. Chen et al. report the structure of a gabapentin-bound brain and heart calcium channel, revealing the gabapentin binding site and isoform-selective binding determinants.

Here the authors use cryo-EM and biochemical analysis to show how the ancillary protein TPR-CHAT regulates the nuclease function of the CRISPR-guided nuclease Cas7-11.

A cryo-EM structure of disease-related human Y145Stop prion protein amyloid fibrils explains species-dependent seeding barriers in prion protein amyloid propagation.

Kottur et al. present high-resolution structures of SARS-CoV-2 nsp14 N7-MTase that will aid in the development of new antivirals against this and other pathogenic coronaviruses.

AlphaFold2 predictions, X-ray crystallography and cryo-EM analyses reveal how related human glycoproteins GP2 and uromodulin catch pathogenic bacteria by presenting a high-mannose glycan that acts as a decoy for fimbrial adhesin FimH.