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A comprehensive proteomics screen reveals that the m6A RNA modification attracts and repels factors that control mammalian mRNA homeostasis. Cover by Erin Dewalt, image from Yon Marsh / Alamy Stock Photo. (p 870)
The cellular crosstalk between different classes of regulatory noncoding RNAs has reached a new spatial dimension. Jiang et al. reveal an essential role of a nuclear-paraspeckle-organizing long noncoding RNA and its protein partners in regulating the first steps of microRNA biogenesis.
PCSK9 enhances LDL cholesterol (LDL-c) levels by escorting the liver LDL receptor (LDLR) to endosomes and lysosomes for degradation. PCSK9 monoclonal antibodies and RNA-antisense formulations are effective in reducing LDL cholesterol in patients. The recent structural identification of a novel pocket in PCSK9 paves the way to the future development of orally active small-molecule hypocholesterolemic drugs.
C-type inactivation is a process by which ion flux through a voltage-gated K+ channel is regulated at the selectivity filter. A recent structure of the Kv1.2 channel provides a view into the structural changes of the selectivity filter during C-type inactivation.
PERK is a major sensor of the unfolded protein response controlling cell fate under endoplasmic reticulum (ER) stress. A new study reveals an additional step for optimal PERK signaling, involving the binding of CNPY2 to PERK's luminal domain. The PERK–CNPY2 axis was shown to enhance cell death under ER stress in vivo influence liver disease.
Five protein complexes, CI–CV, form the oxidative phosphorylation electron transport chain in the mitochondrial membrane and can be found organized into supercomplexes (SCs): I+III2+IV, or respirasome; I+III2; III2+IV; and CV2. Letts and Sazanov review current knowledge on the structure, assembly and function of respiratory SCs.
Cryo-EM and X-ray crystallography to determine the mammalian RNA Pol II–DSIF complex structure maps DSIF's polymerase, DNA-template and transcript contacts that facilitate transcription elongation.
The lncRNA NEAT1, a key component of paraspeckles, interacts with RNA-binding proteins, including NONO and PSF, and affects global pri-miRNA processing by recruiting the Drosha–DGCR8 Microprocessor.
Crystal structures of unprocessed and mature crRNA-bound LbaCas13a shed light upon catalytic residues involved in crRNA maturation and mechanisms blocking Cas13a nuclease activity before target-RNA binding.
In vitro and in vivo data show that ER protein CNPY2 initiates the PERK–CHOP signaling pathway to trigger the unfolded protein response (UPR) and contributes to hepatic steatosis.
p53 oscillations in response to DNA damage lead to oscillatory p53 DNA-binding dynamics, whereas post-transcriptional mechanisms are responsible for the differences in gene expression dynamics.
PCSK9 binds to and promotes degradation of LDLR, thus regulating serum levels of LDL. An accessible groove in PCSK9, adjacent to the LDLR-binding site, can be targeted by peptides that disrupt the LDLR interaction.
A Shaker Kv-channel V478W mutant shows enhanced C-type inactivation with disruption of the outermost K+ site in the selectivity filter (IS1). The crystal structure of Kv1.2-2.1 bearing the equivalent mutation reveals an empty IS1.
Cryo-EM structures of two late-stage assembly intermediates of the human mitoribosomal large subunit reveal the timing of rRNA folding and protein incorporation during the final steps of ribosomal maturation and identify two new assembly factors.
A comprehensive proteomics screen for ‘reader’ proteins that recognize m6A-modified RNA reveals that the modification both promotes and prevents the binding of factors that control mRNA homeostasis in mammalian cells.
