A5088375349- RNA and protein synthesis mechanisms
- RNA Research and Splicing
- RNA modifications and cancer
- Viral Infections and Immunology Research
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
Johns Hopkins University
2019-2024
Howard Hughes Medical Institute
2019-2024
Johns Hopkins Medicine
2019
Translation of problematic sequences in mRNAs leads to ribosome collisions that trigger a series quality control events including rescue, degradation the stalled nascent polypeptide, and targeting mRNA for decay (No Go Decay or NGD). Using reverse genetic screen yeast, we identify Cue2 as conserved endonuclease is recruited ribosomes promote NGD. Ribosome profiling biochemistry provide strong evidence cleaves within A site colliding ribosome. We demonstrate NGD primarily proceeds via...
Key protein adapters couple translation to mRNA decay on specific classes of problematic mRNAs in eukaryotes. Slow decoding non-optimal codons leads codon-optimality-mediated (COMD) and prolonged arrest at stall sites no-go (NGD). The identities the factors underlying these processes mechanisms by which they respond translational distress remain open areas investigation. We use carefully designed reporter perform genetic screens functional assays
The decay of messenger RNA with a premature termination codon by nonsense-mediated (NMD) is an important regulatory pathway for eukaryotes and essential in mammals. NMD typically triggered the ribosome terminating at stop that aberrantly distant from poly-A tail. Here, we use fluorescence screen to identify factors involved Saccharomyces cerevisiae. In addition known factors, including entire UPF family (UPF1, UPF2, UPF3), as well NMD4 EBS1, function posttermination recycling characterize...
Summary R ibosome-associated Q uality C ontrol (RQC) pathways protect cells from toxicity caused by incomplete protein products resulting translation of damaged or problematic mRNAs. Extensive work in yeast has identified highly conserved mechanisms that lead to the degradation faulty mRNA and partially synthesized polypeptide. Here, we used CRISPR-Cas9-based screening search for additional RQC strategies mammals. We found failed leads specific silencing initiation on message. This negative...
Abstract The decay of messenger RNA with a premature termination codon (PTC) by nonsense mediated (NMD) is an important regulatory pathway for eukaryotes and essential in mammals. NMD typically triggered the ribosome terminating at stop that aberrantly distant from poly-A tail. Here, we use fluorescence screen to identify factors involved S. cerevisiae . In addition known factors, including entire UPF family (UPF1, UPF2 UPF3), as well NMD4 EBS1 , function post-termination recycling...
Abstract Translation of problematic sequences in mRNAs leads to ribosome collisions that trigger a sequence quality control events including rescue, degradation the stalled nascent polypeptide via Ribosome-mediated Quality Complex (RQC), and targeting mRNA for decay (No Go Decay or NGD). Previous studies provide strong evidence existence an endonuclease involved process NGD though identity extent which it contributes remain unknown. Using reverse genetic screen yeast, we identify Cue2 as...
Abstract Key protein adapters couple translation to mRNA decay on specific classes of problematic mRNAs in eukaryotes. Slow decoding non-optimal codons leads codon-optimality-mediated (COMD) and prolonged arrest at stall sites no-go (NGD). The identities the factors underlying these processes mechanisms by which they respond translational distress remain open areas investigation. We use carefully-designed reporter perform genetic screens functional assays S. cerevisiae . characterize roles...