Publications by authors named "K M Senn"

Article 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.
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Pre-mRNA splicing, the removal of introns and ligation of flanking exons, is a crucial step in eukaryotic gene expression. The spliceosome, a macromolecular complex made up of five small nuclear RNAs (snRNAs) and dozens of proteins, assembles on introns via a complex pathway before catalyzing the two transesterification reactions necessary for splicing. All of these steps have the potential to be highly regulated to ensure correct mRNA isoform production for proper cellular function.

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Pre-mRNA splicing is catalyzed in two steps: 5' splice site (SS) cleavage and exon ligation. A number of proteins transiently associate with spliceosomes to specifically impact these steps (1 and 2 step factors). We recently identified Fyv6 (FAM192A in humans) as a 2 step factor in ; however, we did not determine how widespread Fyv6's impact is on the transcriptome.

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Small proteins (<50 amino acids) are emerging as ubiquitous and important regulators in organisms ranging from bacteria to humans, where they commonly bind to and regulate larger proteins during stress responses. However, fundamental aspects of small proteins, such as their molecular mechanism of action, downregulation after they are no longer needed, and their evolutionary provenance, are poorly understood. Here, we show that the MntS small protein involved in manganese (Mn) homeostasis binds and inhibits the MntP Mn transporter.

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Background: Inclusion body myositis (IBM) is the most frequent type of myositis in elder patients with a slow chronic progression and refractory to treatment. Previous cost of illness (COI) studies in IBM used claims data to estimate direct costs in the US. No evidence exists globally on both direct and indirect costs in IBM from a societal perspective.

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