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Telomerase RNA (TER) is an essential component of the telomerase ribonucleoprotein complex. The mechanism for TER 3'-end processing is highly divergent among different organisms. Here we report a unique spliceosome-mediated TER 3'-end cleavage mechanism in Neurospora crassa that is distinct from that found specifically in the fission yeast Schizosaccharomyces pombe. While the S. pombe TER intron contains the canonical 5'-splice site GUAUGU, the N. crassa TER intron contains a non-canonical 5'-splice site AUAAGU that alone prevents the second step of splicing and promotes spliceosomal cleavage. The unique N. crassa TER 5'-splice site sequence is evolutionarily conserved in TERs from Pezizomycotina and early branching Taphrinomycotina species. This suggests that the widespread and basal N. crassa-type spliceosomal cleavage mechanism is more ancestral than the S. pombe-type. The discovery of a prevalent, yet distinct, spliceosomal cleavage mechanism throughout diverse fungal clades furthers our understanding of TER evolution and non-coding RNA processing.
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http://dx.doi.org/10.1038/ncomms7105 | DOI Listing |
Mol Biol Cell
September 2025
Department of Life Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel.
The ESCRT machinery mediates membrane remodeling in fundamental cellular processes including cytokinesis, endosomal sorting, nuclear envelope reformation, and membrane repair. Membrane constriction and scission is driven by the filament-forming ESCRT-III complex and the AAA-ATPase VPS4. While ESCRT-III-driven membrane scission is generally established, the mechanisms governing the assembly and coordination of its twelve mammalian isoforms in cells remain poorly understood.
View Article and Find Full Text PDFJ Am Chem Soc
September 2025
Center of Drug Discovery, State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 211198, China.
The advancement of bioorthogonal cleavage platforms has emerged as a critical frontier in chemical biology, offering precise molecular liberation through physiologically compatible activation mechanisms. Despite its significant potential, ensuring efficacy typically requires rapid reaction kinetics, high-efficiency payload release, and stable reactants; however, relevant reports remain sparse. Herein, we developed a strain-promoted alkyne-nitrone cycloaddition (SPANC)-based click-release chemistry through installation of a carbamate-linked release moiety at the propargyl position of cyclooctyne, triggering a spontaneous elimination following click cycloaddition to achieve efficient payload liberation.
View Article and Find Full Text PDFEMBO J
September 2025
Department of Biology, University of Crete, Vassilika Vouton, Heraklion, 70013, Greece.
In the presence of chromatin bridges in cytokinesis, human cells retain actin-rich structures (actin patches) at the base of the intercellular canal to prevent chromosome breakage. Here, we show that daughter nuclei connected by chromatin bridges are under mechanical tension that requires interaction of the nuclear membrane Sun1/2-Nesprin-2 Linker of Nucleoskeleton and Cytoskeleton (LINC) complex with the actin cytoskeleton, and an intact nuclear lamina. This nuclear tension promotes accumulation of Sun1/2-Nesprin-2 proteins at the base of chromatin bridges and local enrichment of the RhoA-activator PDZ RhoGEF through PDZ-binding to cytoplasmic Nesprin-2 spectrin repeats.
View Article and Find Full Text PDFNat Commun
September 2025
CSSB Centre for Structural Systems Biology, Deutsches Elektronen Synchroton DESY, Leibniz Institute of Virology, University of Lübeck, Hamburg, Germany.
In coronavirus (CoV) infection, polyproteins (pp1a/pp1ab) are processed into non-structural proteins (nsps), which largely form the replication/transcription complex (RTC). The polyprotein processing and complex formation is critical and offers potential therapeutic targets. However, the interplay of polyprotein processing and RTC-assembly remains poorly understood.
View Article and Find Full Text PDFBiochem J
September 2025
Cancer Research UK Scotland Institute, Glasgow, G61 1BD, U.K.
RNA cap formation on RNA polymerase II transcripts is regulated by cellular signalling pathways during development and differentiation, adaptive and innate immune responses, during the cell cycle and in response to oncogene deregulation. Here, we discuss how the RNA cap methyltransferase, RNA guanine-7 methyltransferase (RNMT), functions to complete the 7-methyl-guanosine or m7G cap. The mechanisms by which RNMT is regulated by signalling pathways, co-factors and other enzymes are explored.
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