A5061026747- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Peptidase Inhibition and Analysis
- Ubiquitin and proteasome pathways
- Genetics and Neurodevelopmental Disorders
- Viral Infections and Immunology Research
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- Trace Elements in Health
- Neurological disorders and treatments
- Genomics and Rare Diseases
- Biochemical and Molecular Research
- Fungal and yeast genetics research
- Parkinson's Disease Mechanisms and Treatments
- Nuclear Structure and Function
Technical University of Munich
2023
Tohoku University
2013-2022
Niigata University
2000-2001
Translation arrest by polybasic sequences induces ribosome stalling, and the product is degraded ribosome-mediated quality control (RQC) system. Here we report that ubiquitination of 40S ribosomal protein uS10 E3 ubiquitin ligase Hel2 (or RQT1) required for RQC. We identify a RQC-trigger (RQT) subcomplex composed RNA helicase-family Slh1/Rqt2, ubiquitin-binding Cue3/Rqt3, yKR023W/Rqt4 The defects in RQC RQT mutants correlate with sensitivity to anisomycin, which stalls at rotated form....
Coupling translation and mRNA decay Gene expression requires messenger RNAs (mRNAs)—DNA-derived blueprints of genes—to be translated by protein-producing ribosomes. The levels mRNAs are tightly regulated, in part controlling their half-lives. In eukaryotic cells, half-life is largely linked to translational efficiency, but the mechanism underlying this link has remained elusive. Buschauer et al. used cryo–electron microscopy RNA sequencing show how a key regulator degradation, Ccr4-Not...
Abstract Translation of aberrant messenger RNAs can cause stalling ribosomes resulting in ribosomal collisions. Collided are specifically recognized to initiate stress responses and quality control pathways. Ribosome-associated facilitates the degradation incomplete translation products requires dissociation stalled ribosomes. A central event is therefore splitting collided by ribosome trigger complex, RQT, an unknown mechanism. Here we show that RQT accessible mRNA presence a neighboring...
18S non-functional rRNA decay (NRD) eliminates with deleterious mutations in the decoding center. Dissociation of 80S ribosome into 40S and 60S subunits is a prerequisite step for degradation rRNA. However, mechanisms by which recognized dissociated remain elusive. Here, we report that sequential ubiquitination ribosomes crucial subunit dissociation. NRD requires Mag2-mediated monoubiquitination followed Hel2- Rsp5-mediated K63-linked polyubiquitination uS3 at 212th lysine residue....
Abstract Dom34-Hbs1 stimulates degradation of aberrant mRNAs lacking termination codons by dissociating ribosomes stalled at the 3′ ends and plays crucial roles in Nonstop Decay (NSD) No-Go (NGD). In dom34 Δ mutant, nonstop mRNA is degraded sequential endonucleolytic cleavages induced a ribosome end. Here, we report that ribosome-associated Asc1/RACK1 required for cleavage end mutant cells. facilitates truncated GFP-Rz absence Dom34 exosome-dependent decay. depending on its ribosome-binding...
Quality control systems eliminate aberrant proteins derived from m RNA s. Two E 3 ubiquitin ligases, L tn1 and N ot4, are involved in proteasomal protein degradation coupled to translation arrest. Here, we evaluated nonstop arrest products degraded a poly( A ) tail‐independent manner. was found degrade polypeptides lacking termination codon, but not peptidyl‐t , even the absence of ribosome dissociation complex D om34: H bs1. The receptor for activated C kinase ( RACK 1/ ASC 1) identified as...
Abstract Ribosome collisions are recognized by E3 ubiquitin ligase Hel2/ZNF598, leading to RQC (ribosome-associated quality control) and endonucleolytic cleavage degradation of the mRNA termed NGD (no-go decay). in yeast requires Cue2 endonuclease occurs two modes, either coupled (NGDRQC+) or uncoupled (NGDRQC−). This is mediated an unknown mechanism substrate recognition Cue2. Here, we show that binding activity required for NGDRQC− but not NGDRQC+, it involves first N-terminal Cue domains....
In actively translating 80S ribosomes the ribosomal protein eS7 of 40S subunit is monoubiquitinated by E3 ligase Not4 and deubiquitinated Otu2 upon recycling. Despite its importance for translation efficiency exact role structural basis this translational reset poorly understood. Here, analysis cryo-electron microscopy native reconstituted Otu2-bound complexes reveals that engages subunits mainly between ribosome recycling initiation stages. binds to several sites on intersubunit surface are...
The tRNA splicing endonuclease (Sen) complex is located on the mitochondrial outer membrane and splices precursor tRNAs in Saccharomyces cerevisiae. Here, we demonstrate that Sen cleaves mitochondria-localized mRNA encoding Cbp1 (cytochrome b processing 1). Endonucleolytic cleavage of this required two cis-elements: targeting signal stem-loop 652-726-nt region. Mitochondrial localization was for CBP1 mRNA, cleaved directly vitro. We propose which co-translationally localized to mitochondria...
Abstract Ribosome stalling at tandem CGA codons or poly(A) sequences activates quality controls for nascent polypeptides including ribosome-associated control (RQC) and no-go mRNA decay (NGD). In RQC pathway, Hel2-dependent uS10 ubiquitination the RQC-trigger (RQT) complex are essential subunit dissociation, Ltn1-dependent of peptidyl-tRNA in 60S requires Rqc2. Here, we report that polytryptophan induce Rqc2-independent RQC. More than 11 consecutive tryptophan residues induced a manner...
Abstract After translational stalls, colliding eukaryotic ribosomes are cleared through dissociation into subunits by the ribosome quality control trigger complex, RQT, an unknown mechanism. Here we show that RQT requires accessible mRNA and presence of a neighboring ribosome. Cryo-EM several RQT-ribosome complexes revealed structural basis splitting: engages 40S subunit lead can switch between two conformations. We propose mechanistic model in which Slh1 helicase applies pulling force on...
Control of mRNA decay rate is intimately connected to translation elongation but the spatial coordination these events poorly understood. The Ccr4-Not complex initiates through deadenylation and activation decapping. Using a combination cryo-electron microscopy, ribosome profiling stability assays we show recruitment via specific interaction Not5 subunit with ribosomal E-site. This only occurs when lacks accommodated A-site tRNA, indicative low codon optimality. Loss results in inability...
In actively translating 80S ribosomes the ribosomal protein eS7 of 40S subunit is monoubiquitinated by E3 ligase Not4 1,2 and deubiquitinated deubiquitination enzyme Otu2 upon recycling 3 . Despite its importance for general efficiency translation exact role structural basis this specific translational reset are only poorly understood. Here we present biochemical data showing that can engage recycled together with factors ABCE1 Tma64 immediately after 60S dissociation mRNA recycling, it...