Review
Cell Biology
Andrea Putnam, Laura Thomas, Geraldine Seydoux
Summary: This review discusses the current understanding of RNA granules, which are intracellular phase-separated sites of RNA metabolism containing factors for RNA biogenesis and turnover. The authors introduce the concept of incidental condensates, which are tolerated by cells but do not provide additional functionality beyond that of soluble RNP complexes. The article also explores best practices for distinguishing functional RNA granules from incidental condensates.
GENES & DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Markus Grosch, Laura Schraft, Adrian Chan, Leonie Kuechenhoff, Kleopatra Rapti, Anne-Maud Ferreira, Julia Kornienko, Shengdi Li, Michael H. Radke, Chiara Kraemer, Sandra Clauder-Muenster, Emerald Perlas, Johannes Backs, Michael Gotthardt, Christoph Dieterich, Maarten M. G. van den Hoogenhof, Dirk Grimm, Lars M. Steinmetz
Summary: Dilated cardiomyopathy can be repaired using CRISPR gene therapy, but challenges with delivery and off-target effects have limited its applicability. By combining AAVMYO viral vector with CRISPR base editors, we repaired patient mutations in the cardiac splice factor Rbm20. Treatment restored cardiac function and showed no evidence of off-target editing.
NATURE COMMUNICATIONS
(2023)
Article
Cell Biology
Kerri A. Davidson, Mitsutoshi Nakamura, Jeffrey M. Verboon, Susan M. Parkhurst
Summary: Pav and Tum are new molecular components involved in the regulation of nuclear envelope (NE) budding. NE budding, which is independent of nuclear pore, plays important roles in protein quality control, synapse development, and mitochondrial integrity. The actin-bundling activity of Pav is required for the physical and/or organizational aspects of NE buds, providing new insights into the machineries of this alternative nuclear export pathway.
JOURNAL OF CELL BIOLOGY
(2023)
Review
Immunology
Matthew G. Thompson, Matthew T. Sacco, Stacy M. Horner
Summary: RNA modifications play essential roles in cellular surveillance of nucleic acids and controlling gene expression in response to viral infection. These modifications are crucial for a functional antiviral response and maintaining cellular homeostasis. Their coordination contributes to effectively controlling viral infection.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Multidisciplinary Sciences
Lennart Enders, Marton Siklos, Jan Borggrafe, Stefan Gaussmann, Anna Koren, Monika Malik, Tatjana Tomek, Michael Schuster, Jiri Reinis, Elisa Hahn, Andrea Rukavina, Andreas Reicher, Tamara Casteels, Christoph Bock, Georg E. Winter, J. Thomas Hannich, Michael Sattler, Stefan Kubicek
Summary: SMNDC1 is a splicing factor that binds arginine methylation with its Tudor domain. The authors studied the protein's phase-separating behavior and developed small-molecule Tudor domain inhibitors that perturb SMNDC1 function.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Zachary R. Grese, Alliny C. S. Bastos, Lohany D. Mamede, Rachel L. French, Timothy M. Miller, Yuna M. Ayala
Summary: TDP-43 is an RNA-binding protein that forms ribonucleoprotein condensates through liquid-liquid phase separation, playing a central role in regulating gene expression and protein homeostasis. RNA binding promotes TDP-43 condensation through specific interactions, maintaining the liquid-like properties of condensates. Defects in this RNA-mediated activity may contribute to TDP-43-associated pathogenesis, particularly in neurodegenerative disorders such as ALS and frontotemporal dementia.
Article
Hematology
Rhys Wardman, Merve Keles, Ihor Pachkiv, Shruthi Hemanna, Steve Grein, Jennifer Schwarz, Frank Stein, Roxana Ola, Gergana Dobreva, Matthias W. Hentze, Joerg Heineke
Summary: This study reveals that RNA-binding proteins hnRNP H1 and Csde1 play a crucial role in the post-transcriptional regulation of endothelial cells (ECs) in response to TGF-beta stimulation. They maintain EC function and counteract mesenchymal activation by modulating their binding to target RNAs. TGF-beta modifies RNA-protein interaction to fine-tune mesenchymal activation in ECs.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Neurosciences
Muxue Li, Rachel Hamilton, Hannah E. Salapa, Michael C. Levin
Summary: The study demonstrates that primary neurons exposed to pro-inflammatory cytokines and anti-A1 antibodies, characteristic of an MS autoimmune response, exhibit increased A1 mislocalization, stress granule formation, and decreased neurite length, indicating a significant relationship between secreted immune factors, A1 dysfunction, and neuronal damage in a disease-relevant model system.
Article
Biochemistry & Molecular Biology
Lan Fang, Wen Shao, Shu-Tang Zeng, Gui-Xue Tang, Jia-Tong Yan, Shuo-Bin Chen, Zhi-Shu Huang, Jia-Heng Tan, Xiu-Cai Chen
Summary: In this study, a new set of styryl probes were designed and synthesized to improve the detection limit and selectivity of RNA imaging. QUID-2, among these probes, showed the most promising results. It exhibited excellent photostability and low cytotoxicity, and could reveal the global dynamics of RNA in live cells. Moreover, QUID-2 was found to have potential for detecting RNA granules in live cells.
Article
Multidisciplinary Sciences
Meetali Singh, Eric Cornes, Blaise Li, Piergiuseppe Quarato, Loan Bourdon, Florent Dingli, Damarys Loew, Simone Proccacia, Germano Cecere
Summary: In this study, it was found that CSR-1 dependent 22G-RNAs are primarily produced in the cytosol on actively translating mRNAs, and the codon usage of an mRNA regulates the biogenesis of CSR-1 dependent 22G-RNAs.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Toshiyuki Ko, Seitaro Nomura, Shintaro Yamada, Kanna Fujita, Takanori Fujita, Masahiro Satoh, Chio Oka, Manami Katoh, Masamichi Ito, Mikako Katagiri, Tatsuro Sassa, Bo Zhang, Satoshi Hatsuse, Takanobu Yamada, Mutsuo Harada, Haruhiro Toko, Eisuke Amiya, Masaru Hatano, Osamu Kinoshita, Kan Nawata, Hiroyuki Abe, Tetsuo Ushiku, Minoru Ono, Masashi Ikeuchi, Hiroyuki Morita, Hiroyuki Aburatani, Issei Komuro
Summary: This study identifies Htra3 as a critical regulator of cardiac fibrosis and heart failure by maintaining the identity of quiescent cardiac fibroblasts and degrading TGF-beta. These findings provide new insights into the pathogenesis of heart failure and suggest Htra3 as a potential therapeutic target.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Laura Valeria Rios-Barros, Anna Luiza Silva-Moreira, Maria Fatima Horta, Nelder Figueiredo Gontijo, Thiago Castro-Gomes
Summary: Parasitic protozoa cause diseases with significant public health impact by evading the host immune system through various strategies. The complement system, an important effector mechanism, can lead to the elimination of parasites. Parasitic protozoa employ different strategies to avoid complement activation, including regulation and expression of complement system proteins, proteolytic cleavage of complement molecules, formation of physical barriers, and removal of bound complement molecules. This review summarizes the strategies used by parasitic protozoa to block complement activation and discusses new perspectives in this field.
MOLECULAR IMMUNOLOGY
(2022)
Article
Cell Biology
M. Sankaranarayanan, Ryan J. Emenecker, Elise L. Wilby, Marcus Jahnel, Irmela R. E. A. Trussina, Matt Wayland, Simon Alberti, Alex S. Holehouse, Timothy T. Weil
Summary: Ribonucleoprotein condensates can exhibit diverse physical states, with specific proteins, protein-protein interactions, and RNA regulating their properties. In this study, the physical properties of processing bodies (P bodies) in mature Drosophila oocytes were investigated, showing how the arrested state of P bodies supports mRNA storage and how egg activation modulates P body properties to release mRNA for translation in the early embryo. This work provides insight into how the physical states of condensates regulate cellular function in development.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Qiuxia Yan, Peng Zeng, Xiuqin Zhou, Xiaoying Zhao, Runqiang Chen, Jing Qiao, Ling Feng, Zhenjie Zhu, Guozhi Zhang, Cairong Chen
Summary: The study revealed that RBMX is significantly downregulated in bladder cancer tissues and inhibits tumorigenicity and progression through interfering with PKM alternative splicing. This suggests RBMX may serve as a novel prognostic biomarker for clinical intervention in bladder cancer.
Article
Multidisciplinary Sciences
Stephanie J. Zhang, Daniel Duzdevich, Dian Ding, Jack W. Szostak
Summary: Nonenzymatic template-directed RNA copying using chemically activated nucleotides may have played a crucial role in the emergence of genetic information on early Earth. Recent experiments have shown that multiple freeze-thaw cycles in a reaction mixture can facilitate nucleotide activation, synthesis of imidazolium-bridged dinucleotides, and template-directed RNA copying. These findings suggest that environmental fluctuations, such as freeze-thaw cycles, could have been important in prebiotic nucleotide activation and nonenzymatic RNA copying.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)