Publications by authors named "A Hoskins"
Meayamycins are synthetic analogs of the natural product FR901464 and exhibit potent anticancer activity against human cancers. They bind SF3B1 and PHF5A, components of the human spliceosome, and they alter pre-mRNA splicing. Detailed analysis of the active site led us to investigate a narrow pocket within the binding site that surrounds the α,β-unsaturated amide portion of meayamycin.
View Article and Find Full Text PDFArticle Synopsis
- Pre-mRNA splicing involves two key steps: 5' splice site cleavage and the ligation of exons, influenced by specific proteins called first and second step factors.
- Researchers identified Fyv6 (FAM192A in humans) as a second step factor affecting splicing, and their RNA sequencing analysis revealed that its loss activates non-consensus splice sites across the transcriptome.
- High-resolution cryo-electron microscopy showed that Fyv6 interacts uniquely with the Prp22 ATPase and its binding excludes another factor (Yju2), leading to a proposed model where Fyv6 enhances the use of traditional splice sites and aids in exon ligation.
Managing feral water buffalo in the Northern Territory is a formidable challenge. As an introduced species, buffalo are associated with a myriad of biosecurity, economic, cultural and environmental issues ranging from overgrazing, decreased water quality, disease vectors to the destruction of cultural assets. Nevertheless, the buffalo are also a harvestable resource that can support economic development of the region.
View Article and Find Full Text PDFArticle Synopsis
- Splice site recognition plays a crucial role in defining the transcriptome, and drugs like risdiplam and branaplam can modify how U1 snRNP recognizes specific 5' splice sites (5'SS).
- This research identifies a sequential binding mechanism for how branaplam influences the modulation of -1A bulged 5'SS, using advanced techniques like ensemble kinetic measurements and CoSMoS.
- The findings show that branaplam binds to the complex only after U1 snRNP engages with a 5'SS, impacting the formation of stable U1 snRNP/5'SS complexes, highlighting that branaplam interacts with ribonucleoprotein rather than just RNA.
Spliceosome assembly and catalytic site formation (called activation) involve dozens of protein and snRNA binding and unbinding events. The B-complex specific proteins Prp38, Snu23, and Spp381 have critical roles in stabilizing the spliceosome during conformational changes essential for activation. While these proteins are conserved, different mechanisms have been proposed for their recruitment to spliceosomes.
View Article and Find Full Text PDF