Article
Biophysics
Changhong Shi, Xiyan Yang, Jiajun Zhang, Tianshou Zhou
Summary: This study develops a general theoretical framework to explain the complex biochemical process of mRNA life cycle and extract kinetic parameters from experimental data. The framework allows evaluation of the influence of elongation processes on mature RNA distribution, and identifies the optimal elongation noise intensity for achieving the lowest mature RNA noise levels.
BIOPHYSICAL JOURNAL
(2023)
Article
Cell Biology
Suji Lim, Yan Liu, Byung-Ho Rhie, Chun Kim, Hong-Yeoul Ryu, Seong Hoon Ahn
Summary: The study finds that Sus1 is a key factor in linking transcription and mRNA nuclear export. SAGA DUB module and TREX-2 have distinct roles in yeast replicative lifespan. Loss of Sus1 affects growth and lifespan, which depends on TREX-2. Increasing mRNA export factors can rescue the effects.
Article
Multidisciplinary Sciences
Shiladitya Chattopadhyay, Jose Garcia-Martinez, Gal Haimovich, Jonathan Fischer, Aya Khwaja, Oren Barkai, Silvia Gabriela Chuartzman, Maya Schuldiner, Ron Elran, Miriam Rosenberg, Shira Urim, Shubham Deshmukh, Katherine E. Bohnsack, Markus T. Bohnsack, Jose E. Perez-Ortin, Mordechai Choder
Summary: This study reveals the crucial role of nucleocytoplasmic shuttling of yeast mRNA decay factors in regulating both transcription and mRNA decay. The shuttling process is controlled by decaying RNA and is essential for coping with environmental changes.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Ke Zhang, Lisa Miorin, Tadashi Makio, Ishmael Dehghan, Shengyan Gao, Yihu Xie, Hualin Zhong, Matthew Esparza, Thomas Kehrer, Anil Kumar, Tom C. Hobman, Christopher Ptak, Boning Gao, John D. Minna, Zhijian Chen, Adolfo Garcia-Sastre, Yi Ren, Richard W. Wozniak, Beatriz M. A. Fontoura
Summary: The research shows that the virulence factor Nsp1 protein of SARS-CoV-2 interacts with the host messenger RNA (mRNA) export receptor heterodimer NXF1-NXT1, leading to retention of cellular mRNAs in the nucleus during infection. Increasing levels of NXF1 can rescue the Nsp1-mediated mRNA export block and inhibit SARS-CoV-2 infection. Antagonizing the inhibitory function of Nsp1 on mRNA export may represent a strategy to restore proper antiviral host gene expression in infected cells.
Article
Biochemistry & Molecular Biology
Matthew P. Swaffer, Georgi K. Marinov, Huan Zheng, Lucas Fuentes Valenzuela, Crystal Yee Tsui, Andrew W. Jones, Jessica Greenwood, Anshul Kundaje, William J. Greenleaf, Rodrigo Reyes-Lamothe, Jan M. Skotheim
Summary: A fundamental feature of cellular growth is that protein and RNA amounts increase with cell size to maintain constant concentrations. In budding yeast, RNA polymerase II (RNAPII) is identified as the limiting factor scaling mRNA transcription with cell size. The global RNAPII transcription is determined by the mass action recruitment kinetics of unengaged nucle-oplasmic RNAPII to the genome. However, this increase in transcription with size is partially compensated for by a decrease in mRNA decay rates as cells enlarge.
Article
Cell Biology
Jia Fei, Jun Xu, Ziwei Li, Kevin Xu, Dong Wang, George A. Kassavetis, James T. Kadonaga
Summary: NDF is a transcription elongation factor that binds to Pol II and enhances gene expression elongation by a different mechanism than TFIIS.
GENES & DEVELOPMENT
(2022)
Article
Plant Sciences
Kun Xing, Zhao Liu, Le Liu, Jie Zhang, Ghulam Qanmber, Ye Wang, Lisen Liu, Yu Gu, Changsheng Zhang, Shuaijie Li, Yan Zhang, Zuoren Yang
Summary: This study reveals the potential link between m(6)A modification and cotton fiber elongation, and demonstrates that m(6)A methylation regulates the expression of genes related to fiber development by affecting mRNA stability, ultimately affecting cotton fiber elongation.
Article
Biochemistry & Molecular Biology
Yanjie Li, Jixue Li, Jun Wang, David R. Lynch, Xiulong Shen, David R. Corey, Darshan Parekh, Balkrishen Bhat, Caroline Woo, Jonathan J. Cherry, Jill S. Napierala, Marek Napierala
Summary: A novel approach targeting FXN mRNA ends with oligonucleotides has been shown to increase FXN mRNA and protein levels, offering a potential therapeutic avenue for Friedreich's ataxia. The method has been validated in multiple cases and has the ability to upregulate steady-state mRNA levels.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Belen Pacheco-Fiallos, Matthias K. Vorlaender, Daria Riabov-Bassat, Laura Fin, Francis J. O'Reilly, Farja I. Ayala, Ulla Schellhaas, Juri Rappsilber, Clemens Plaschka
Summary: Newly made mRNAs are recognized and organized by the essential TREX complex for nuclear export. Cryo-electron microscopy and tomography structures reveal that mRNAs are recognized through multivalent interactions between TREX subunit ALYREF and mRNP-bound exon junction complexes. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes, providing a framework to understand mRNA biogenesis and export.
Article
Biochemistry & Molecular Biology
Pallabi Mitra, Sneha Banerjee, Chittiraju Khandavalli, Abhijit S. Deshmukh
Summary: This study reports a key modulator of RNAPII activity, TgTFIIS, and elucidates its potential role in early events of transcription and elongation.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2022)
Article
Biochemistry & Molecular Biology
John C. W. Hildyard, Richard J. Piercy
Summary: This manuscript discusses the challenges in quantifying dystrophin gene expression and presents a transcriptional model to explain the coupling of long transcription time with short mature mRNA half-life. The effects of this model on cellular transcriptional dynamics are explored, and key implications for the study of dystrophin gene expression, focusing on both conventional (qPCR) and next-gen (RNAseq) approaches, are discussed.
Article
Multidisciplinary Sciences
Georgia Katsioudi, Rene Dreos, Enes S. Arpa, Sevasti Gaspari, Angelica Liechti, Miho Sato, Christian H. Gabriel, Achim Kramer, Steven A. Brown, David Gatfield
Summary: The study demonstrates the importance of nonsense-mediated mRNA decay (NMD) in physiological control, particularly in regulating the circadian clock and gene expression.
Article
Immunology
Matthew T. Witkowski, Soobeom Lee, Eric Wang, Anna K. Lee, Alexis Talbot, Chao Ma, Nikolaos Tsopoulidis, Justin Brumbaugh, Yaqi Zhao, Kathryn G. Roberts, Simon J. Hogg, Sofia Nomikou, Yohana E. Ghebrechristos, Palaniraja Thandapani, Charles G. Mullighan, Konrad Hochedlinger, Weiqiang Chen, Omar Abdel-Wahab, Justin Eyquem, Iannis Aifantis
Summary: Aifantis and colleagues used leukemic cell lines to identify novel regulators of CD19 expression in B-ALL. They found that the transcriptional activator ZNF143 plays a critical role in CD19 promoter activation, while the RNA-binding protein NUDT21 limits CD19 expression through the regulation of CD19 mRNA polyadenylation and stability. Deletion of NUDT21 in B-ALL cells increased CD19 expression and sensitivity to CAR-T and blinatumomab. Clinical findings showed that upregulation of NUDT21 coincided with CD19 loss in B-ALL patients at disease relapse.
Article
Cell Biology
Samuel H. Keller, Hao Deng, Bomyi Lim
Summary: This study examines how enhancers, promoters, and gene body composition affect the rate of RNA Pol II elongation through a live imaging assay in single cells. The research findings reveal that promoters and exonic gene lengths do not impact the elongation rate, while enhancers and the presence of long introns have a significant effect on the speed of RNA Pol II movement across genes. Additionally, it was observed that RNA Pol II elongation rate accelerates after the transcriptional onset of nuclear cycle 14 in Drosophila embryos. These findings provide insights into the mechanisms that regulate the dynamic RNA Pol II elongation rate.
Article
Cell Biology
Ashish Kumar, Yuanzhi Lyu, Yuichi Yanagihashi, Chanikarn Chantarasrivong, Vladimir Majerciak, Michelle Salemi, Kang-Hsin Wang, Tomoki Inagaki, Frank Chuang, Ryan R. Davis, Clifford G. Tepper, Kazushi Nakano, Chie Izumiya, Michiko Shimoda, Ken-ichi Nakajima, Alexander Merleev, Zhi-Ming Zheng, Mel Campbell, Yoshihiro Izumiya
Summary: This study reveals the nuclear microenvironment of Kaposi sarcoma-associated herpesvirus (KSHV) and its role in regulating the latency-lytic replication switch. Viral long non-coding RNAs interact with CHD4 to control KSHV reactivation.
Article
Multidisciplinary Sciences
Sonia Jimeno, Rosario Prados-Carvajal, Maria Jesus Fernandez-Avila, Sonia Silva, Domenico Alessandro Silvestris, Martin Endara-Coll, Judit Domingo-Prim, Fernando Mejias-Navarro, Guillermo Rodriguez-Real, Amador Romero-Franco, Silvia Jimeno-Gonzalez, Sonia Barroso, Valeriana Cesarini, Andres Aguilera, Angela Gallo, Neus Visa, Pablo Huertas
Summary: Specific RNA-related factors, including the RNA-editing enzyme ADAR2, play important roles in DNA repair. The researchers found that RNA editing is involved in the response to DNA damage, with a phenomenon called the RNA Editing DAmage Response (REDAR) being observed. REDAR relies on the checkpoint kinase ATR and the recombination factor CtIP, and depletion of ADAR2 leads to increased cellular sensitivity to genotoxic agents and impaired homologous recombination.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Pedro Ortega, Jose Antonio Merida-Cerro, Ana G. Rondon, Belen Gomez-Gonzalez, Andres Aguilera
Summary: DNA double-strand breaks (DSBs) are highly harmful DNA lesions and their repair is crucial for cell viability and genome integrity. Studies have debated whether DNA-RNA hybrids formed at DSBs promote or interfere with recombinational repair. High levels or unresolved DNA-RNA hybrids at breaks interfere with homologous recombination, regardless of how the DSB is generated.
Review
Biochemistry & Molecular Biology
Aleix Bayona-Feliu, Andres Aguilera
Summary: DNA replication and transcription must be coordinated to prevent Transcription-Replication Conflicts (TRCs) that could stall replication forks. Chromatin homeostasis plays a key role in the cellular response to conflicts and in the preservation of genome integrity.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Article
Genetics & Heredity
Pedro Ortega, Belen Gomez-Gonzalez, Andres Aguilera
Summary: Recent studies have shown the critical role of chromatin in both the occurrence and repair of DNA damage, particularly double-strand breaks. It is considered as a guardian of genome stability, which is altered in cancer cells.
Article
Biochemistry & Molecular Biology
Elena Galati, Maria C. Bosio, Daniele Novarina, Matteo Chiara, Giulia M. Bernini, Alessandro M. Mozzarelli, Maria L. Garcia-Rubio, Belen Gomez-Gonzalez, Andres Aguilera, Thomas Carzaniga, Marco Todisco, Tommaso Bellini, Giulia M. Nava, Gianmaria Frige, Sarah Sertic, David S. Horner, Anastasia Baryshnikova, Caterina Manzari, Anna M. D'Erchia, Graziano Pesole, Grant W. Brown, Marco Muzi-Falconi, Federico Lazzaro
Summary: This study identifies VID22 as a novel regulator of genome integrity in yeast cells, involved in DNA double-strand break repair and protection of G4-DNA structures. Loss of VID22 leads to increased levels of endogenous DNA damage and hypersensitivity to G4-stabilizing ligands.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
Despoina Sakellariou, Sara Thornby Bak, Esin Isik, Sonia Barroso, Antonio Porro, Andres Aguilera, Jiri Bartek, Pavel Janscak, Javier Pena-Diaz
Summary: The study reveals that the mismatch repair protein MutS beta is enriched at telomeres in ALT cancer cells, preventing the accumulation of G-quadruplex (G4) structures and R-loops, thus maintaining telomere integrity during alternative lengthening of telomeres.
Review
Genetics & Heredity
Elena Lopez-Jimenez, Cristina Gonzalez-Aguilera
Summary: This article discusses the importance of chromatin organization in maintaining gene expression regulation and cell identity, as well as the causes and mechanisms of chromatin disorganization during cell division. Additionally, it highlights the impact of these chromatin alterations on gene expression control and diseases related to cell proliferation.
Article
Multidisciplinary Sciences
Seong-Su Han, Kuo-Kuang Wen, Maria L. Garcia-Rubio, Marc S. Wold, Andres Aguilera, Wojciech Niedzwiedz, Yatin M. Vyas
Summary: This study identifies a crucial role for WASp in the DNA stress-resolution pathway, specifically in promoting the function of Replication Protein A at replication forks after DNA damage. Deficiency of WASp leads to RPA dysfunction, resulting in genomic instability.
NATURE COMMUNICATIONS
(2022)
Article
Genetics & Heredity
Juan Carlos Canas, Maria Luisa Garcia-Rubio, Alicia Garcia, Francisco Antequera, Belen Gomez-Gonzalez, Andres Aguilera
Summary: The chromatin modifier Rtt109 plays a crucial role in the metabolism and repair of DNA-RNA hybrids and R-loops, with histone acetylation helping to prevent DNA damage and promote repair.
Article
Cell Biology
Esther Marchena-Cruz, Lola P. Camino, Jay Bhandari, Sonia Silva, Jose Javier Marqueta-Gracia, Shahad A. Amdeen, Cristina Guillen-Mendoza, Maria L. Garcia-Rubio, Jose M. Calderon-Montano, Xiaoyu Xue, Rosa Luna, Andres Aguilera
Summary: Unscheduled R loops can lead to genome instability, a characteristic of cancer cells. By targeting activation-induced cytidine deaminase (AID), 59 potential candidates causing R loops were identified, which are enriched in factors involved in chromatin, transcription, RNA biogenesis, and other processes. The study suggests that various gene dysfunctions can affect R-loop homeostasis through different mechanisms, thereby altering cell physiology.
Review
Biochemistry & Molecular Biology
Belen Gomez-Gonzalez, Andres Aguilera
Summary: Double-strand breaks (DSBs) are highly harmful DNA damages that have significant effects on cell proliferation and genome integrity. Recent studies have shown that DSBs can enhance the formation of DNA-RNA hybrids, called break-induced RNA-DNA hybrids (BIRDHs). The source and impact of BIRDHs are still unresolved questions.
Article
Multidisciplinary Sciences
Aleix Bayona-Feliu, Emilia Herrera-Moyano, Nibal Badra-Fajardo, Ivan Galvan-Femenia, Maria Eugenia Soler-Oliva, Andres Aguilera
Summary: The chromatin network prevents genomic instability and mutagenic signatures associated with cancer by inhibiting R-loops and transcription-replication conflicts.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Environmental Sciences
Sergio Munoz, Sonia Barroso, Javier Marqueta-Gracia, Maria Eugenia Soler, Andres Aguilera
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)
Meeting Abstract
Environmental Sciences
Andres Aguilera, Yesenia Rodriguez, Philip Hanawalt, Karlene A. Cimprich
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
(2022)
Article
Oncology
Belen Gomez-Gonzalez, Gaetana Sessa, Aura Carreira, Andres Aguilera
Summary: In a recent report, a new interaction between BRCA2 and DDX5 at DNA breaks has been revealed, promoting unwinding of DNA-RNA hybrids for repair. Interestingly, this interaction is impaired in cells expressing the BRCA2(T207A) missense variant found in breast cancer patients.
MOLECULAR & CELLULAR ONCOLOGY
(2021)
