Volume 27 Issue 9, 2 September 2020

Translation and mRNA decay are tightly connected processes governing protein production, and their regulation involves an elaborate network of protein factors and sequence elements. A massively parallel RNA-based reporter system now reveals regulatory pathways triggered by 5′ UTR elements and allows dissection of the interplay between translation and mRNA decay.

The cell surface protein CD4 acts as a coreceptor for incoming HIV particles. However, the expression of CD4 in HIV-producing cells is detrimental to virus propagation and pathogenicity. To solve this issue, the viral accessory protein Nef forces CD4 endocytosis and targets it for lysosomal degradation. Structural elucidation of the AP-2–Nef–CD4 complex shows how Nef connects CD4 to the clathrin endocytic machinery, revealing a potential new target for anti-HIV therapy.

Visualizing siRNA targeting of single mRNAs in living cells reveals that passing ribosomes temporarily unfold the mRNA, exposing it to siRNA recognition. This effect is due to the slow reorganization of many weak, suboptimal interactions within the mRNA.

The nuclear piRNA pathway safeguards genome integrity in the germline by silencing transposable elements. Three recent studies have identified new players in the mammalian pathway. Two of these, TEX15 and SPOCD1, might provide a link between piRNA-guided complexes that recognize genomic targets and the molecular machinery that induces DNA methylation and transcriptional repression during mouse spermatogenesis.

Disulfide-bond formation between a cysteine pair at the groove and C-terminal α-helix of the anti-apoptotic protein BFL-1 operates as a redox switch that controls the accessibility of the protein’s anti-apoptotic pocket, which is important for the regulation of pro-apoptotic BCL-2 family members.

Live-cell single-molecule imaging reveals that the rate-limiting step in AGO2-mediated mRNA cleavage frequently involves unmasking of target sites by translating ribosomes.

A combination of structural and protein-chemistry approaches along with phylogenetic analyses provide insights into the specific activities of mouse tubulin tyrosine ligase-like enzymes as initiases or elongases of glutamylation.

Massively parallel reporter assays from a synthetic mRNA library identify sequence features of 5′ UTRs that control mRNA translatability and reveal ribosome-dependent and ribosome-independent mRNA-surveillance pathways.

Crystallography and mutagenesis analyses examine how HIV-1 Nef interacts with AP2 to enable CD4 binding and downregulation and reveal the role of a Nef pocket that is also involved in downregulation of class I MHC.

A crystal structure of bacterial multidrug transporter LmrP reveals the presence of a lipid inside the substrate binding cavity, with MD simulations and mutational analyses suggesting it could be involved in broad substrate specificity.

A combination of cell-based and biochemical approaches reveals how oncogenic fusion protein SS18-SSX directs BAF complexes to H2AK119Ub-modified nucleosomes to remodel chromatin at cancer-specific gene targets.

Two nanobodies that bind SARS-CoV-2 spike RBD are shown to block interaction with receptor ACE2 and thus neutralize the virus, and have an additive effect with antibody CR3022.

Cryo-EM structures of HIV-1 capsid in tubular assemblies feature intrinsically curved and asymmetric hexamers and provide insight into cyclophilin A binding.

Structures of HIV-1 capsid protein (CA) in tubular assemblies, determined by MAS-NMR, reveal the basis of CA’s conformational plasticity.