Article
Cell Biology
Isabella N. Brown, M. Carmen Lafita-Navarro, Maralice Conacci-Sorrell
Summary: The nucleolus plays a crucial role in protein synthesis by producing new ribosomes. In cancer, nucleolar activity is heightened due to increased demand for protein synthesis. The transcription factor MYC promotes nucleolar activity and understanding and potentially inhibiting aberrant nucleolar activity in cancer cells could lead to novel therapeutics.
Review
Cell Biology
Marianne Mercer, Seoyeon Jang, Chunyang Ni, Michael Buszczak
Summary: Regulation of mRNA translation is crucial for germ cell development and function across species, involving specific RNA binding proteins. These proteins are conserved and play similar roles in germ cells of various species, highlighting the importance of understanding the mechanisms controlling mRNA translation in germ cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Editorial Material
Hematology
Jean-Francois Peyron
Summary: In MYC-driven B-cell lymphoma, activation of the ribosome biogenesis checkpoint triggers an apoptotic response through p53-induced, proteasome-dependent degradation of MCL-1.
Review
Cell Biology
Chunyang Ni, Michael Buszczak
Summary: The integrity of biological systems depends on a balance between interdependent elements at different levels. Ribosome biogenesis plays a crucial role in cell and organismal biology. Recent studies have shown that ribosome production is dynamically regulated to maintain homeostasis in response to changing environmental conditions and stress. There are significant differences in ribosome production and protein synthesis levels among cells and tissues of multicellular organisms. This review focuses on the mechanisms that link ribosome biogenesis with cellular and organismal physiology, including coordination between different steps in ribosome biogenesis, the impact of MYC and mTOR, and the changes in ribosome production during stem cell differentiation.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yu Gan, Jun Deng, Qian Hao, Yingdan Huang, Tao Han, Jin-Guo Xu, Min Zhao, Litong Yao, Yingying Xu, Jianping Xiong, Hua Lu, Chunmeng Wang, Jiaxiang Chen, Xiang Zhou
Summary: In this study, it was found that UTP11 plays a crucial role in the biosynthesis of 18S ribosomal RNAs (rRNA) by binding to the pre-rRNA processing factor, MPP10. UTP11 is overexpressed in human cancers and is associated with poor prognoses. Depletion of UTP11 inhibits cancer cell growth through p53-dependent and -independent mechanisms, while UTP11 overexpression promotes cancer cell growth and progression. The study also reveals that UTP11 depletion triggers nucleolar stress and enhances ferroptosis, contributing to the inhibition of cancer cell survival and growth.
Article
Cell Biology
Shannon E. Weeks, Sarah C. Kammerud, Brandon J. Metge, Heba A. AlSheikh, David A. Schneider, Dongquan Chen, Shi Wei, James A. Mobley, Akinyemi I. Ojesina, Lalita A. Shevde, Rajeev S. Samant
Summary: Triple-negative breast cancer patients with upregulated Wnt/beta-catenin signaling often have poor clinical prognoses. A greater abundance of nucleoli was observed in specimens from TNBC patients compared to non-TNBC, showing a direct relationship with nuclear beta-catenin. Further investigations revealed the differential functional relevance of the nucleolus in TNBC versus non-TNBC cells.
CELL DEATH & DISEASE
(2021)
Review
Cell Biology
Shane M. Breznak, Noor M. Kotb, Prashanth Rangan
Summary: The ability of ribosomes to translate mRNAs into proteins is crucial for life. Reduction in ribosome levels can have tissue-specific effects on cell fate and developmental transitions, leading to ribosomopathies. Model systems like Drosophila and C. elegans oogenesis have been used to study the impact of dysregulated ribosome homeostasis on stem cell differentiation and development. This review explores the influence of ribosome levels on stem cells, the role of ribosomal modifications and protein paralogs in development, and the ways in which cells with perturbed ribosome biogenesis are eliminated.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Article
Cell Biology
Rasool Saghaleyni, Magdalena Malm, Noah Moruzzi, Jan Zrimec, Ronia Razavi, Num Wistbacka, Hannes Thorell, Anton Pintar, Andreas Hober, Fredrik Edfors, Veronique Chotteau, Per-Olof Berggren, Luigi Grassi, Aleksej Zelezniak, Thomas Svensson, Diane Hatton, Jens Nielsen, Jonathan L. Robinson, Johan Rockberg
Summary: Recombinant protein production causes stress on cellular metabolism, limiting both yield and quality. Our study shows that EPO-producing cells have higher metabolism and oxidative phosphorylation compared to non-secreting cells. The expression pattern of ribosomal genes also depends on the recombinant protein and production rate. Manipulating genes related to negative regulation of ER stress can enhance EPO production.
Article
Cell Biology
H. Broder Schmidt, Zane A. Jaafar, B. Erik Wulff, Jason J. Rodencal, Kibeom Hong, Mohammad O. Aziz-Zanjani, Peter K. Jackson, Manuel D. Leonetti, Scott J. Dixon, Rajat Rohatgi, Onn Brandman
Summary: This study reveals that oxaliplatin induces liquid-liquid demixing of nucleoli at clinically relevant concentrations, leading to cell-cycle arrest, shutdown of Pol I-mediated transcription, and cell death. This mechanism offers a general approach for drugging cellular processes linked to biomolecular condensates.
Article
Multidisciplinary Sciences
Yu Zhao, Jay Rai, Hong Li
Summary: Pseudouridine is vital to the central dogma as it is enriched in ribosomal, spliceosomal, transfer, and messenger RNA. However, the impact of pseudouridine on the molecular apparatus, such as the ribosome, remains unclear due to a lack of structures without this modification. This study investigated the translation of a hypopseudouridylated ribosome initiated by the internal ribosome entry site (IRES) elements, revealing the loss of pseudouridine-mediated interactions and the link between functional defects and modification loss.
Article
Biochemistry & Molecular Biology
Benjamin Lau, Zixuan Huang, Nikola Kellner, Shuangshuang Niu, Otto Berninghausen, Roland Beckmann, Ed Hurt, Jingdong Cheng
Summary: This article reports nine nucleolar pre-60S cryo-EM structures from Chaetomium thermophilum, one of which clarifies the mechanism of 5S RNP incorporation into the early pre-60S. Successive assembly states then represent how helicases Dbp10 and Spb4, and the Pumilio domain factor Puf6 act in series to surveil the gradual folding of the nearby 25S rRNA domain IV. Finally, the methyltransferase Spb1 methylates a universally conserved guanine nucleotide in the A-loop of the peptidyl transferase center, thereby licensing further maturation.
Article
Multidisciplinary Sciences
Karla T. Falcon, Kristin E. N. Watt, Soma Dash, Ruonan Zhao, Daisuke Sakai, Emma L. Moore, Sharien Fitriasari, Melissa Childers, Mihaela E. Sardiu, Selene Swanson, Dai Tsuchiya, Jay Unruh, George Bugarinovic, Lin Li, Rita Shiang, Annita Achilleos, Jill Dixon, Michael J. Dixon, Paul A. Trainor
Summary: This study investigates the importance of ribosomal RNA (rRNA) transcription in craniofacial development and the implications of disruptions in this process. The researchers discovered that high expression of Pol I subunits in neuroepithelium and neural crest cells (NCCs) sustains elevated rRNA transcription, supporting the high levels of protein translation in these cells. However, disruptions in rRNA synthesis in NCCs can lead to p53 protein accumulation, NCC apoptosis, and craniofacial anomalies. Compound mutations in Pol I subunits further exacerbate these anomalies. Mechanistically, diminished rRNA synthesis causes an imbalance between rRNA and ribosomal proteins, affecting the binding of these proteins with Mdm2 and p53. This study highlights the critical role of rRNA transcription in craniofacial development and its specific sensitivities to disruptions in certain congenital craniofacial disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
David P. Dannheisig, Jana Baechle, Jasmin Tasic, Marina Keil, Astrid S. Pfister
Summary: Ribosomes are essential for cell growth and survival, and their biogenesis process in nucleoli is controlled by RNA polymerases I-III and various processing factors. Nucleolar stress triggered by impaired ribosome biogenesis can lead to cell cycle arrest and apoptosis, and is used in modern anti-cancer therapies but may also contribute to diverse pathological conditions. Activation of the Wnt/beta-Catenin pathway is observed when nucleolar stress is induced, suggesting a compensatory mechanism to sustain ribosome biogenesis.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Matthew John Eastham, Andria Pelava, Graeme Raymond Wells, Nicholas James Watkins, Claudia Schneider
Summary: Two of the four human ubiquitin-encoding genes express ubiquitin as an N-terminal fusion precursor polypeptide, with either RPS27a or RPL40 at the C-terminus. RPS27a and RPL40 are important for the induction of p53, suggesting their role in the coordination of ribosome production, ubiquitin levels, and p53 signaling. Knockdown of both RPS27a and RPL40 induces p53 and is needed for rRNA production in MCF7 and LNCaP cells, indicating their cell type-dependent role in p53 signaling and consistent role in ribosome biogenesis.
Article
Gastroenterology & Hepatology
Xiao-Mei Yang, Xiao-Qi Wang, Li-Peng Hu, Ming-Xuan Feng, Yao-Qi Zhou, Dong-Xue Li, Jun Li, Xiao-Cao Miao, Yan-Li Zhang, Hui-Zhen Nie, Shan Huang, Qiang Xia, Xue-Li Zhang, Shu-Heng Jiang, Zhi-Gang Zhang
Summary: This study discovered that HEATR1 is downregulated by insulin-like growth factor 1-mammalian target of rapamycin complex 1-specificity protein 1 signaling, and it plays a crucial regulatory role in ribosome biogenesis and proteome homeostasis to promote HCC development.
Correction
Biochemistry & Molecular Biology
Siew Chin Chan, Chih-Wei Tung, Chia-Wei Lin, Yun-Shiuan Tung, Po-Min Wu, Pei-Hsun Cheng, Chuan-Mu Chen, Shang-Hsun Yang
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Suyuan Liu, Meiling Tan, Jiangxue Cai, Chenxuan Li, Miaoxin Yang, Xiaoxiao Sun, Bin He
Summary: This study reveals that the antibiotic doxycycline effectively inhibits NLRP3 inflammasome activation by targeting mitochondrial translation and mtDNA synthesis, offering potential for the treatment of NLRP3-related diseases.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)
Article
Biochemistry & Molecular Biology
Hao Liu, Nana Li, Ge Kuang, Xia Gong, Ting Wang, Jun Hu, Hui Du, Minxuan Zhong, Jiashi Guo, Yao Xie, Yang Xiang, Shengwang Wu, Yiling Yuan, Xinru Yin, Jingyuan Wan, Ke Li
Summary: Protectin D1 (PTD1) improves hepatic steatosis, inflammation and fibrosis in a NASH mouse model by inhibiting the activation of TLR4 downstream signaling pathway, possibly through upregulation of IRAK-M expression, suggesting a potential new treatment for NASH.
FREE RADICAL BIOLOGY AND MEDICINE
(2024)