A5045436151- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Biochemical and Molecular Research
- Nuclear Structure and Function
- Galectins and Cancer Biology
- RNA regulation and disease
- Calcium signaling and nucleotide metabolism
- Fungal and yeast genetics research
- Advanced Proteomics Techniques and Applications
- Bioinformatics and Genomic Networks
- Fatty Acid Research and Health
- Environmental Science and Water Management
- Biopolymer Synthesis and Applications
- Toxin Mechanisms and Immunotoxins
- Fungal Biology and Applications
University of Zurich
2018-2025
ETH Zurich
2019-2025
Aarhus University
2020
Abstract Protein phosphorylation is the best characterized post-translational modification that regulates almost all cellular processes through diverse mechanisms such as changing protein conformations, interactions, and localization. While inventory for sites across different species has rapidly expanded, their functional role remains poorly investigated. Here, we combine 537,321 phosphosites from 40 eukaryotic to identify highly conserved hotspot regions within domain families. Mapping...
Eukaryotic ribosome precursors acquire translation competence in the cytoplasm through stepwise release of bound assembly factors, and proofreading their functional centers. In case pre-60S, these steps include removal placeholders Rlp24, Arx1 Mrt4 that prevent premature loading ribosomal protein eL24, protein-folding machinery at polypeptide exit tunnel (PET), stalk, respectively. Here, we reveal sequential ATPase GTPase activities license factors Rei1 Yvh1 to trigger removal. Drg1-ATPase...
Disordered extensions at the termini and short internal insertions distinguish eukaryotic ribosomal proteins (r-proteins) from their anucleated archaeal counterparts. Here, we report an NMR structure of such a eukaryotic-specific segment (ESS) in r-protein eS26 complex with escortin Tsr2. The reveals how ESS attracts Tsr2 specifically to importin:eS26 complexes entering nucleus order trigger non-canonical RanGTP-independent disassembly. then sequesters released prevents rebinding importin,...
ARS2 is a conserved protein centrally involved in both nuclear RNA productive and destructive processes. To map features of promoting decay, we utilized two different reporters, one which depends on direct tethering for its degradation. In cases, triggers degradation phenotype aided by interaction with the poly(A) tail exosome targeting (PAXT) connection. Interestingly, C-terminal amino acids ARS2, responsible binding 5'cap complex (CBC), become dispensable when directly tethered to reporter...
Abstract Productive ribosomal RNA (rRNA) compaction during ribosome assembly necessitates establishing correct tertiary contacts between distant secondary structure elements. Here, we quantify the response of yeast proteome to low temperature (LT), a condition where aberrant mis-paired folding intermediates accumulate. We show that, at LT, cells globally boost production their machinery. find that LT-induced factor, Puf6, binds nascent catalytic RNA-rich subunit interface within 60S...
Abstract Ribosome abundance in changing environments is governed by biogenesis and degradation, but the underlying mechanisms regulating these opposing processes remain unknown. Here we show that Suppressor of Tom1 (Stm1), a dormancy factor protecting cytosolic ribosomes during starvation, has an unexpected function to promote ribosome exponential growth conditions. Indeed, Stm1 transiently localizes nucleolus engages with pre-ribosomal particles. upregulates transcription ribosomal protein...
Construction of the eukaryotic ribosome is a complex process in which nascent ribosomal RNA (rRNA) emerging from Polymerase I hierarchically folds into native three-dimensional structure. Modular assembly individual domains through interactions with proteins and myriad factors permit efficient disentanglement error-prone folding process. Following these dynamic events, long-range tertiary are orchestrated to compact rRNA. A combination genetic, biochemical, structural studies now providing...
Abstract The process of eukaryotic ribosome assembly stretches across the nucleolus, nucleoplasm and cytoplasm, therefore relies on efficient nucleocytoplasmic transport. In yeast, import machinery delivers ~140,000 ribosomal proteins every minute to nucleus for assembly. At same time, export facilitates translocation ~2000 pre-ribosomal particles through ~200 nuclear pore complexes (NPC) into cytoplasm. Eukaryotic also requires >200 conserved factors, which transiently associate with...
The ribotoxin α-sarcin belongs to a family of ribonucleases that cleave the sarcin/ricin loop (SRL), critical functional rRNA element within large ribosomal subunit (60S), thereby abolishing translation. Whether targets SRL only in mature 60S subunits remains unresolved. Here, we show that, yeast, can SRLs late pre-ribosomes containing 25S but not nucleolar/nuclear 27S pre-rRNA vivo. Conditional expression is lethal, does impede early processing, nuclear export and cytoplasmic maturation...
Abstract Mechanisms by which G-patch activators tune the processive multi-tasking ATP-dependent RNA helicase Prp43 (DHX15 in humans) to productively remodel diverse RNA:protein complexes remain elusive. Here, a comparative study between herein and previously characterized activators, Tma23 Pxr1, respectively, defines segments that organize function during ribosome assembly. In addition activating G-patch, we discover an inhibitory segment within I-patch, restrains ATPase activity....
Abstract Protein phosphorylation is the best characterized post-translational modification that regulates almost all cellular processes through diverse mechanisms such as changing protein conformations, interactions, and localization. While inventory for sites across different species has rapidly expanded, their functional role remains poorly investigated. Here, we have combined 537,321 phosphosites from 40 eukaryotic to identify highly conserved “hotspot” regions within domain families....