MRC Laboratory of Molecular Biology

The tRNA‐Modification Geranyl‐2‐Thiouridine Enables RNA‐Lipid Association

The packaging of RNA in lipid nanoparticles for protection and delivery was key for the development of mRNA vaccines and therapeutics. Formulation requires the addition of a variety of lipids (including cationic) in high amounts to form complexes with the negatively charged RNA....

Prion-like transmission of human tau strains in the mouse brain

Abstract Most neurodegenerative diseases are thought to spread through the brain by prion-like mechanisms, in which filamentous protein assemblies self-propagate by templated seeding 1 . Distinct conformations of amyloid filaments may provide the physical basis for the strains th...

Cotranslational membrane protein biogenesis by an EMC-bound translocon

Secretory and membrane protein biogenesis occurs at ribosome-bound translocons in the endoplasmic reticulum (ER) membrane. Translocons consist of the Sec61 protein-conducting channel and various maturation factors including chaperones, modification enzymes and membrane insertases...

MemBrain v2: an end-to-end tool for the analysis of membranes in cryo-electron tomography

Abstract Cryo-electron tomography provides unique insights into macromolecular complexes in their native environments, yet membrane analysis remains a major bottleneck due to low signal-to-noise ratios, missing wedge artifacts and the complexity of membrane-associated particles....

Response of the replisome to araA and araC suggests a mechanism for arabinosyl nucleoside tolerance

Arabinosyl (ara) nucleoside analogues such as vidarabine (araA) and cytarabine (araC) are antimetabolites known to inhibit DNA polymerases in isolation. However, their effects on DNA synthesis catalysed by the multi-protein replisome remain unknown. Here, we uncover a central rol...

John Derek Smith

Abstract In the 1950s and 1960s John Smith pioneered the studies of RNA sequence and function and, in doing so, laid the foundations for the subsequent immense flowering and power of genomic sequencing as it is practised today. First and foremost John was a meticulous experimenta...

Sequential restriction of SNARE-mediated fusion by the COPII inner coat and SNARE chaperones

Abstract SNARE-mediated fusion requires assembly of four SNARE domains (R, Qa, Qb, and Qc) distributed across two membranes, with an SM (Sec1/Munc-18 family) chaperone catalyzing this assembly. We investigated topological requirements for the four SNAREs that mediate ER-Golgi fus...

Mapping the NFYA 3′UTR landscape identifies alternative polyadenylation as a targetable vulnerability in prostate cancer

Abstract Background Alternative polyadenylation (APA) is increasingly recognized as a pervasive oncogenic mechanism that reshapes post-transcriptional gene regulation and promotes tumor aggressiveness. Whether APA contributes to the dysregulation of NFYA —encoding the regulatory...

Reversible epiblast regionalization determines differentiation potential of human pluripotent stem cells

Abstract Although human pluripotent stem cells (hPSCs) can generate all tissues of the body, hPSCs in vitro frequently exhibit differentiation biases or failure that pose substantial challenges for disease modeling and regenerative medicine. The origins of these biases remain inc...