Review
Biochemistry & Molecular Biology
Yoshitaka Matsuo, Toshifumi Inada
Summary: Genetic mutations, mRNA processing errors, and lack of charged tRNAs can slow down or inhibit translating ribosomes. Monitoring systems are in place to detect and dispose of incomplete nascent chains and aberrant translation products to prevent accumulation and maintain protein homeostasis. Yeast models have been instrumental in uncovering the molecular mechanisms of these co-translational quality control systems.
Article
Biochemistry & Molecular Biology
Ashis Kumar Pradhan, Ganapathi Kandasamy, Upasana Chatterjee, Anushree Bharadwaj, Sam J. Mathew, R. Jurgen Dohmen, R. Palanimurugan
Summary: This study reveals that the degradation of Orf1p requires the coordinated action of both ribosome-associated and cytosolic protein quality control factors.
Review
Microbiology
Lorenzo Eugenio Leiva, Victor Zegarra, Gert Bange, Michael Ibba
Summary: Nucleotides are essential for biological processes in the cell, playing key roles in molecular biology and regulating metabolic pathways. They are dynamic, interact with each other, and provide feedback to the cell's metabolic state, adapting to environmental and growth challenges. Intracellular nucleotides fine-tune the activity of RNA polymerase, synthesis of tRNAs, mRNA translation, and assembly of ribosomes involved in protein synthesis. The ribosome acts as a molecular hub where nucleotides encounter and regulate the cell's state.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)
Review
Biochemistry & Molecular Biology
Lana Buzuk, Doris Hellerschmied
Summary: The Golgi apparatus plays a crucial role in the secretory pathway of eukaryotic cells, processing proteins and organizing their transportation to other cellular compartments. It is involved in cell surface formation, cell polarity, cell-cell communication, immune signaling, DNA damage response, and mitosis. Maintaining Golgi integrity and protein homeostasis is essential, as Golgi fragmentation and dysfunction are linked to neurodegenerative diseases and certain cancers. Recent studies have revealed the importance of ubiquitin signaling in maintaining Golgi integrity and protein quality control, similar to the endoplasmic reticulum. Ubiquitination helps prevent the accumulation of toxic protein aggregates and regulates Golgi structural rearrangements in response to cellular stress.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Paul Whitley, Brayan Grau, James C. Gumbart, Luis Martinez-Gil, Ismael Mingarro
Summary: The endoplasmic reticulum (ER) plays a crucial role in eukaryotic cells by facilitating the entry and distribution of newly synthesized proteins. Membrane-integrated amino acids are typically non-polar/hydrophobic and form alpha-helical transmembrane (TM) helices for survival in the ER's non-aqueous environment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Ken Ikeuchi, Nives Ivic, Robert Buschauer, Jingdong Cheng, Thomas Froehlich, Yoshitaka Matsuo, Otto Berninghausen, Toshifumi Inada, Thomas Becker, Roland Beckmann
Summary: This study reveals the impact of Otu2-driven deubiquitylation of ribosomal protein eS7 on translational efficiency and provides insights into its role in translation reset. The authors found that eS7 in actively translating 80S ribosomes is monoubiquitinated by the E3 ligase Not4 and deubiquitinated by Otu2 upon ribosomal subunit recycling. Cryo-electron microscopy analysis showed that Otu2 mainly binds to the 40S subunit surface at sites not occupied by other factors.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Momoko Narita, Timo Denk, Yoshitaka Matsuo, Takato Sugiyama, Chisato Kikuguchi, Sota Ito, Nichika Sato, Toru Suzuki, Satoshi Hashimoto, Iva Machova, Petr Tesina, Roland Beckmann, Toshifumi Inada
Summary: The authors discovered that collided ribosomes play a crucial role in quality control mechanisms. By ubiquitination, the collided ribosomes are marked and the quality control complex is recruited for subunit dissociation. The ubiquitination activity and K63-linked polyubiquitination of uS10 are critical for ribosome dissociation.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Lihui Wang, Yihong Ye
Summary: Recent studies have uncovered a set of translocon-associated quality control strategies for eliminating polypeptides stuck in protein-conducting channels in the endoplasmic reticulum and mitochondria.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Fuxing Zeng, Xin Li, Melissa Pires-Alves, Xin Chen, Christopher W. Hawk, Hong Jin
Summary: In this study, it was found that the yeast Rbg1/Tma46 facilitates translation by suppressing ribosome pausing, thereby ensuring normal growth. Deletion of Rbg1 exacerbates growth defects caused by translation stalling, while also stabilizing mRNAs and binding to the ribosome and A-tRNA. These interactions are critical for maintaining orderly translation.
Article
Multidisciplinary Sciences
Jordan S. Kesner, Ziheng Chen, Peiguo Shi, Alexis O. Aparicio, Michael R. Murphy, Yang Guo, Aditi Trehan, Jessica E. Lipponen, Yocelyn Recinos, Natura Myeku, Xuebing Wu
Summary: Translation is widespread in noncoding regions, especially in ageing, neurodegeneration and cancer. Although most tumor-specific antigens are products of noncoding translation, the resulting polypeptides are often nonfunctional, but necessary for the birth of new coding sequences. The mechanisms underlying the surveillance of translation in noncoding regions and the evolution of escaped polypeptides with new functions are unclear. Functional polypeptides derived from annotated noncoding sequences often localize to membranes. Our study reveals a fail-safe mechanism for monitoring unwanted translation and suggests a biochemical route for the membrane localization of newly evolved proteins.
Article
Multidisciplinary Sciences
Xiaolu Wang, Yao Li, Xiaojie Yan, Qing Yang, Bing Zhang, Ying Zhang, Xinxin Yuan, Chenhao Jiang, Dongxing Chen, Quanyan Liu, Tong Liu, Wenyi Mi, Ying Yu, Cheng Dong
Summary: A study reveals that the E3 ligase Pirh2 degrades aberrant nascent polypeptides by targeting the C-terminal polyalanine degrons. The crystal structure of Pirh2 bound to the polyAla/C-degron is presented, demonstrating the recognition of a C-terminal A/S-X-A-A motif by Pirh2 for substrate degradation.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Yoshitaka Matsuo, Toshifumi Inada
Summary: The study finds that Hel2 preferentially binds to pre-engaged secretory ribosome-nascent chain complexes, especially under signal recognition particle (SRP) deficient conditions. Deletion of Hel2 exacerbates mitochondrial defects caused by insufficient SRP, leading to mistargeting of secretory proteins into mitochondria. These insights shed light on risk management in the secretory pathway for maintaining cellular protein homeostasis.
Article
Biochemistry & Molecular Biology
Rebeca Ibarra, Heather R. Borror, Bryce Hart, Richard G. Gardner, Gary Kleiger
Summary: The yeast PQC ubiquitin ligase San1 contains multiple substrate binding sites along its polypeptide chain, showing specificity for unique misfolded proteins and enabling the formation of high affinity ubiquitin ligase-substrate complexes.
Letter
Cell Biology
Michela Damizia, Gian Mario Moretta, Peter De Wulf
Summary: Transcription factor p53 supports genomic stability, cellular health, and survival. p53 mutations, misexpression, or dysregulation are common in cancers. RioK1, acting as an upstream factor, determines p53 activity at the DNA, RNA, and protein levels. Overexpression of RIOK1 is an alternative mechanism for activating p53.
CELL DEATH DISCOVERY
(2023)
Review
Microbiology
Colin R. Harwood, Yoshimi Kikuchi
Summary: Most bacteria reproduce by binary fission and may be considered immortal, although they age due to damage to DNA and proteins. DNA damage can often be repaired, but proteins have a functional lifespan and require specific degradation processes. Proteases play crucial roles in various cellular functions in different parts of the cell.
FEMS MICROBIOLOGY REVIEWS
(2022)
Editorial Material
Genetics & Heredity
Katharine H. Wrighton
NATURE REVIEWS GENETICS
(2019)
Editorial Material
Neurosciences
Grant Otto
NATURE REVIEWS NEUROSCIENCE
(2019)
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Microbiology
Katharine H. Wrighton
NATURE REVIEWS MICROBIOLOGY
(2020)
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Biotechnology & Applied Microbiology
Katharine H. Wrighton
NATURE REVIEWS DRUG DISCOVERY
(2020)
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Microbiology
Katharine H. Wrighton
NATURE REVIEWS MICROBIOLOGY
(2020)
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Biotechnology & Applied Microbiology
Katharine H. Wrighton
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(2020)
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NATURE REVIEWS GENETICS
(2020)
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Genetics & Heredity
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NATURE REVIEWS GENETICS
(2021)
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Genetics & Heredity
Katharine H. Wrighton
NATURE REVIEWS GENETICS
(2021)
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Genetics & Heredity
Katharine H. Wrighton
NATURE REVIEWS GENETICS
(2022)
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Biochemistry & Molecular Biology
Katharine H. Wrighton
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
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Biotechnology & Applied Microbiology
Katharine H. Wrighton
NATURE BIOTECHNOLOGY
(2022)
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Katharine H. Wrighton
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
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Biochemistry & Molecular Biology
Katharine H. Wrighton
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Editorial Material
Oncology
Katharine H. Wrighton