Researchers from The Universities of Manchester and Birmingham have identified the exact nerve cells in the brain that drive important behavioural changes in female fruit flies after they mate.The dis...

DNA codon frequencies and mRNA expression levels are the main predictors of protein abundance. In the absence of environmental perturbation neither gene-body methylation, tRNA abundance nor ribosome-associated transcript levels add appreciable information. The impact of constitutive gene-body methyl …

He and colleagues develop a METTL3-based RNA base-editing screening strategy to identify functional N6-methyladenosine (m6A) sites that are important for prostate cancer cells and validate the role of...

Heparan sulfate proteoglycans facilitate the assembly of clusters of glycoRNAs and cell surface RNA-binding proteins, which negatively modulate VEGF-A signalling and angiogenesis.

Kretov et al. introduce RBPscan, an RNA-editing-based platform that measures how RNA-binding proteins engage their targets in living cells. This approach quantifies the binding strength of protein-RNA...

Site-specific insertion of gene-sized DNA fragments remains an unmet need in the genome editing field. IS110-family serine recombinases have recently been shown to mediate programmable DNA recombinati...

Dierks and Schwartz discuss the m6A surveillance model, proposing that m6A flags “undesirable” intron-less RNAs (e.g., transposons) for decay. This provides a mechanism to distinguish “legitimate” spliced mRNAs and potentially suppress harmful RNA.

A monthly journal publishing high-quality, peer-reviewed research on all topics related to RNA and its metabolism in all organisms

Protein degradation by the proteasome is central to cellular homeostasis and has been studied extensively using biochemical and structural studies. Despite an in-depth understanding of core proteolytic activity, it has remained largely unresolved how individual proteasomes process substrates inside living cells where many substrate types and co-factors exist. Here, we establish a live-cell single-molecule imaging approach that enables direct visualization and quantification of protein degradation by individual proteasomes. Using this approach, we find that substrate identity, folding and protein-protein interaction have a surprisingly modest impact on processing efficiency, whereas the mode of substrate engagement greatly impacts substrate processing; degradation initiated from protein termini typically proceeds rapidly and with high processivity, whereas internal engagement constitutes a distinct processing mode that exhibits poor processivity and a specific requirement for the AAA+ family ATPase p97/VCP. Furthermore, degradation initiated from opposite termini proceeds with asymmetric rates in a sequence-dependent manner, demonstrating that directionality is an important feature of proteasomal processing in vivo. Notably, poly-glutamine substrates associated with neurodegenerative disease are efficiently degraded from one terminus but resist degradation when engaged from the opposite terminus, highlighting the importance of substrate engagement mode. Together, our results show that different modes of substrate engagement lead to different proteasomal processing outcomes in vivo and revise the prevailing view of the proteasome as a uniform degradation machine. ### Competing Interest Statement The authors have declared no competing interest.

Nature Communications - The vaccinia virus produces mRNA lacking the 5′ m7G cap structure. These uncapped mRNAs have long poly(A) leaders and dominate late in infection, suggesting a novel...

Therapeutic suppressor tRNAs are engineered to broaden their target range in vivo.

Artificial intelligence boosts individual scientists’ output, citations and career progression, but collectively narrows research diversity and reduces collaboration, concentrating work in data-rich a...