The spliceosome removes introns from messenger RNA precursors (pre-mRNA). Decades
of biochemistry and genetics combined with recent structural studies of the spliceosome …

Cryogenic electron microscopy (cryo-EM) enables structure determination of
macromolecular objects and their assemblies. Although the techniques have been …

Macromolecular complexes that exhibit continuous forms of structural flexibility pose a
challenge for many existing tools in cryo-EM single-particle analysis. We describe a new …

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed
after comprehensive genetic testing, primarily of protein-coding genes. Large genome …

Precursor messenger RNA (pre-mRNA) splicing is an essential step in the flow of
information from DNA to protein in all eukaryotes. Research over the past four decades has …

Electron cryo-microscopy analyzes the structure of proteins and protein complexes in
vitrified solution. Proteins tend to adsorb to the air-water interface in unsupported films of …

Recent studies have highlighted that splicing patterns are frequently altered in cancer and
that mutations in genes encoding spliceosomal proteins, as well as mutations affecting the …

Several macromolecular machines collaborate to produce eukaryotic messenger RNA. RNA
polymerase II (Pol II) translocates along genes that are up to millions of base pairs in length …

This chapter describes algorithmic advances in the RELION software, and how these are
used in high-resolution cryo-electron microscopy (cryo-EM) structure determination. Since …

Human γ-secretase is an intra-membrane protease that cleaves many different substrates.
Aberrant cleavage of Notch is implicated in cancer, while abnormalities in cutting amyloid …