Article
Biology
Milda Mickute, Kotryna Kvederaviciute, Aleksandr Osipenko, Raminta Mineikaite, Saulius Klimasauskas, Giedrius Vilkaitis
Summary: The study presents a novel chemo-enzymatic approach using RNA 2'-O-methyltransferases to append an adapter to target RNA for sequencing library preparation. This method efficiently identifies RNA species, avoiding misdetection of highly-structured RNA. The findings provide valuable resources for RNA-centered regulatory network studies and could potentially advance the analysis of eukaryotic and prokaryotic ssRNAs.
Article
Biochemical Research Methods
Delilah Jewel, Rachel E. E. Kelemen, Rachel L. L. Huang, Zeyu Zhu, Bharathi Sundaresh, Xiaofu Cao, Kaitlin Malley, Zeyi Huang, Muhammad Pasha, Jon Anthony, Tim van Opijnen, Abhishek Chatterjee
Summary: Virus-assisted directed evolution of tRNAs (VADER) allows for the efficient enrichment of active and orthogonal tRNA mutants from naive libraries in mammalian cells. Using this method, improved mutants of Methanosarcina mazei pyrrolysyl-tRNA and a bacterial tyrosyl-tRNA were obtained. The most efficient mutant pyrrolysyl-tRNA showed specific activity for mammalian cells, suggesting improved interaction with the unique mammalian translation machinery.
Review
Cell Biology
Hara Kang, Yun Ji Ga, Soo Hyun Kim, Young Hoon Cho, Jung Won Kim, Chaeyeon Kim, Jung-Yong Yeh
Summary: RNA has become a revolutionary tool in battling emerging infectious diseases, particularly in response to the COVID-19 pandemic. RNAi therapeutics have shown potential in reducing disease-associated genes, and nucleic acid-based therapies have emerged as alternative treatments. However, there are obstacles to overcome in the use of siRNA-based antiviral therapies, including off-target effects and drug resistance.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Biochemical Research Methods
Samuel J. Hendel, Matthew D. Shoulders
Summary: Directed evolution experiments are traditionally conducted using in vitro systems, bacteria, or yeast, but there is now a shift towards using mammalian cells as the setting for such experiments. This shift has the potential to expand the scope and functionality of evolved targets, but also presents new challenges and opportunities for high-impact research.
Review
Biochemistry & Molecular Biology
Zhiqi Deng, Liqun Ma, Peiyu Zhang, Hongliang Zhu
Summary: Small RNAs play significant roles in plant development, stress response, and antiviral immunity. This paper reviews the mechanisms by which small RNAs regulate viral defense in plants and the strategies employed by viruses to overcome host immune responses. Additionally, the current development status of new virus defense applications based on small RNA silencing is discussed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Gregory Mathez, Valeria Cagno
Summary: The majority of antivirals target viral proteins, but RNA is gaining attention as a new and promising antiviral target. This article discusses methods for identifying RNA-targeting compounds, including determination of RNA structures and in silico screening. It also reviews small molecules that target specific RNA elements in viruses like SARS-CoV-2 and HIV.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Alesia A. Levanova, Mirka Lampi, Kiira Kalke, Veijo Hukkanen, Minna M. Poranen, Katri Eskelin
Summary: This study developed an AF4 method for efficient purification of enzymatically produced small interfering RNA molecules and demonstrated the potential of AF4 in separating short RNA molecules.
Article
Immunology
Santiago Fontenla, Mauricio Langleib, Eduardo de la Torre-escudero, Maria Fernanda Dominguez, Mark W. Robinson, Jose Tort
Summary: MicroRNAs (miRNAs) are important regulators of gene expression. This study investigated the expression patterns of miRNAs during different developmental stages of the liver fluke Fasciola hepatica. The study found variations in miRNA expression across the stages and identified potential target genes. The most highly expressed miRNAs were found to be involved in host immune response and infection establishment and maintenance. Additionally, fragments derived from tRNA processing and vtRNAs were detected, suggesting their involvement in the host-parasite interaction.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Wan -Xiang Li, Shou-Wei Ding
Summary: The antiviral defense directed by the RNAi pathway employs distinct specificity and effector mechanisms compared with other immune responses. The specificity of antiviral RNAi is programmed by siRNAs processed from virus-derived double-stranded RNA by Dicer endonuclease. Argonaute-containing RNA-induced silencing complex loaded with the viral siRNAs acts as the effector to mediate specific virus clearance by RNAi. Recent studies have provided evidence for the production and antiviral function of virus-derived siRNAs in both undifferentiated and differentiated mammalian cells infected with a range of RNA viruses when the cognate virus-encoded suppressor of RNAi (VSR) is rendered nonfunctional. In this review, we discuss the function, mechanism, and evolutionary origin of the validated mammalian VSRs and cell culture assays for their identification.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Enzo Z. Poirier, Michael D. Buck, Probir Chakravarty, Joana Carvalho, Bruno Frederico, Ana Cardoso, Lyn Healy, Rachel Ulferts, Rupert Beale, Caetano Reis e Sousa
Summary: The discovery of a Dicer isoform called antiviral Dicer provides protection for tissue stem cells against RNA viruses, shedding light on the molecular regulation of antiviral RNAi in mammalian innate immunity. Different cell-intrinsic antiviral pathways can be tailored to the differentiation status of cells.
Article
Cell Biology
Weihong Xie, Chenqiu Zhang, Zheyu Wang, Hui Chen, Tonghui Gu, Tao Zhou, Yaoxing Wu, Fan Xia, Min Li, Jun Wang, Renjie Jiao, Jun Cui, Shouheng Jin
Summary: ATG4B negatively regulates human antiviral immune responses by promoting autophagic degradation of TBK1. Inhibiting ATG4B can enhance host defense against viral infection and provide a potential therapy target.
Article
Biology
Hideyuki Nakanishi
Summary: Synthetic mRNAs produced by in vitro transcription can express any transgenes without the risk of insertional mutagenesis. Preclinical studies have developed translational regulation systems to ensure high efficacy and low adverse effects by producing the appropriate amount of therapeutic proteins.
Article
Biochemical Research Methods
Xilei Ai, Shan Zhou, Meiyi Chen, Feng Du, Yi Yuan, Xin Cui, Juan Dong, Xin Huang, Zhuo Tang
Summary: RNA editing is a reversible therapeutic approach for correcting pathogenic mutations. This study presents a small molecule-inducible RNA editing strategy by incorporating aptazymes into ADAR-based RNA editing technology. The aptazymes trigger self-cleavage in the presence or absence of small molecules, allowing controlled RNA editing. This strategy improves the safety and potential clinical applications of RNA editing technology.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Shunsuke Kawasaki, Hiroki Ono, Moe Hirosawa, Takeru Kuwabara, Shunsuke Sumi, Suji Lee, Knut Woltjen, Hirohide Saito
Summary: The scarcity of qualified RNA-binding proteins hinders the development of artificial translational regulators and synthetic gene circuits. Here, the authors repurposed CRISPR-Cas proteins as translational regulators to build synthetic circuits. CARTRIDGE (Cas-Responsive Translational Regulation Integratable into Diverse Gene control) is a versatile molecular toolkit for mammalian synthetic biology that uses Cas proteins as translational modulators in mammalian cells. By linking multiple Cas-mediated translational modulators, artificial circuits like logic gates, cascades, and half-subtractor circuits can be designed and built.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
K. Shanmugha Rajan, Katerina Adler, Tirza Doniger, Smadar Cohen-Chalamish, Noa Aharon-Hefetz, Saurav Aryal, Yitzhak Pilpel, Christian Tschudi, Ron Unger, Shulamit Michaeli
Summary: The effect of RNA modifications on the survival ability of Trypanosoma brucei, the parasite causing sleeping sickness, in insect and mammalian hosts is unclear. This study mapped pseudouridinylation sites on different RNAs in the parasite using two genome-wide approaches. The researchers found differential levels of pseudouridinylation on noncoding RNAs in the two life stages of the parasite, suggesting a potential role in regulating important biological processes.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Tomoko Takahashi, Yuko Nakano, Koji Onomoto, Fuminori Murakami, Chiaki Komori, Yutaka Suzuki, Mitsutoshi Yoneyama, Kumiko Ui-Tei
NUCLEIC ACIDS RESEARCH
(2018)
Article
Multidisciplinary Sciences
Sarah C. Atkinson, Michelle D. Audsley, Kim G. Lieu, Glenn A. Marsh, David R. Thomas, Steven M. Heaton, Jason J. Paxman, Kylie M. Wagstaff, Ashley M. Buckle, Gregory W. Moseley, David A. Jans, Natalie A. Borg
SCIENTIFIC REPORTS
(2018)
Letter
Multidisciplinary Sciences
Niluka D. Wasalathanthri
Article
Genetics & Heredity
Tomoko Takahashi, Yuko Nakano, Koji Onomoto, Mitsutoshi Yoneyama, Kumiko Ui-Tei
Article
Cell Biology
Steven M. Heaton, Sarah C. Atkinson, Melissa N. Sweeney, Sundy N. Y. Yang, David A. Jans, Natalie A. Borg
Review
Biochemistry & Molecular Biology
Tomoko Takahashi, Kumiko Ui-Tei
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Tomoko Takahashi, Yuko Nakano, Koji Onomoto, Mitsutoshi Yoneyama, Kumiko Ui-Tei
NUCLEIC ACIDS RESEARCH
(2020)
Article
Cell Biology
Sundy N. Y. Yang, Sarah C. Atkinson, Michelle D. Audsley, Steven M. Heaton, David A. Jans, Natalie A. Borg
Article
Biochemistry & Molecular Biology
Sarah C. Atkinson, Steven M. Heaton, Michelle D. Audsley, Oded Kleifeld, Natalie A. Borg
Summary: The study reveals a novel interaction between TRIM25 and another protein in the RLR pathway, which cooperatively enhances IFN-beta production. Additionally, the research uncovers a new mechanism by which influenza A virus NS1 suppresses host antiviral defense.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Steven M. Heaton, Paul R. Gorry, Natalie A. Borg
Summary: Antiretroviral therapy (ART) is effective in reducing HIV-1 infection. However, the emergence of treatment-refractory variants remains a challenge. HIV-1 uses cellular helicases, including DDX3X, to facilitate its replication. Exploring these helicases may reveal new therapeutic targets and help prevent viral escape.
TRENDS IN MICROBIOLOGY
(2023)
Article
Genetics & Heredity
Shohei Kojima, Satoshi Koyama, Mirei Ka, Yuka Saito, Erica Parrish, Mikiko Endo, Sadaaki Takata, Misaki Mizukoshi, Keiko Hikino, Atsushi Takeda, Asami Gelinas, Steven Heaton, Rie Koide, Anselmo F. Kamada, Michiya Noguchi, Michiaki Hamada, Biobank Japan Project Consortium, Yoichiro Kamatani, Yasuhiro Murakawa, Kazuyoshi Ishigaki, Yukio Nakamura, Kaoru Ito, Chikashi Terao, Yukihide Momozawa, Nicholas F. Parrish
Summary: MEGAnE is a new tool for detecting and genotyping mobile element variants (MEVs) from short-read whole-genome sequencing datasets. This tool has revealed population-specific differences in MEVs and their impact on gene expression variation and disease risk. The integration of MEVs with expression quantitative trait loci (eQTL) maps has shown that MEVs regulate tissue-specific gene expression and contribute to genome diversification and traits.
Review
Pharmacology & Pharmacy
S. M. Heaton
Summary: The therapeutic gap between new emerging infectious diseases and effective treatments can potentially be bridged by targeting host factors involved in the replication strategies of evolutionarily diverse viruses. XPO1 inhibition has shown efficacy in suppressing replication of various viruses, with one XPO1 inhibitor entering clinical trials for treating SARS-CoV-2 infection. This review examines strategies and challenges in targeting XPO1-mediated nuclear export for treating different virus infections.
DRUGS OF THE FUTURE
(2021)
Review
Immunology
Steven M. Heaton
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2019)