Review
Immunology
Carissa Ikka Pardamean, Ting-Ting Wu
Summary: Viruses have the ability to alter host gene expression, with Kaposi sarcoma-associated herpesvirus having two proteins that obstruct this process. The proteins SOX and ORF10 play a role in inhibiting host gene expression through different mechanisms. Studies on these proteins, along with research on a related rodent virus, provide insights into their roles in viral pathogenesis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Helen M. Gunter, Senel Idrisoglu, Swati Singh, Dae Jong Han, Emily Ariens, Jonathan R. Peters, Ted Wong, Seth W. Cheetham, Jun Xu, Subash Kumar Rai, Robert Feldman, Andy Herbert, Esteban Marcellin, Romain Tropee, Trent Munro, Tim R. Mercer
Summary: Researchers describe a method using long-read sequencing and a custom bioinformatic pipeline to analyze the quality of mRNA vaccines. This streamlined approach allows for comprehensive evaluation of mRNA vaccine attributes and chemistry, making it a potential central technology for the development and manufacture of mRNA drugs.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Vladimir Despic, Samie R. R. Jaffrey
Summary: The mRNA cap structure is a major site of dynamic mRNA methylation, with Cap1 and Cap2 forms depending on the presence of 2'-O-methylation on the first transcribed nucleotide or both the first and second transcribed nucleotides, respectively. The identity and function of Cap2-containing mRNAs are currently unclear.
Review
Biochemistry & Molecular Biology
Hyun-Sun Park, Jongbok Lee, Hyun-Shik Lee, Seong Hoon Ahn, Hong-Yeoul Ryu
Summary: The relationship between transcription and aging has been extensively studied. The nuclear mRNA export plays a crucial role in cellular aging and age-related neurodegenerative disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Katherine L. B. Borden
Summary: Recent research has identified the eukaryotic translation initiation factor eIF4E as a significant player in mRNA splicing, which affects the structure and function of proteins. eIF4E interacts physically with the spliceosome and certain transcripts containing introns, suggesting its direct involvement in splicing events. Furthermore, eIF4E influences the production of essential components of the splicing machinery, leading to broader impacts on splicing. These findings shed light on the post-transcriptional control and eIF4E-driven cancers.
Review
Microbiology
Lorenzo Eugenio Leiva, Assaf Katz
Summary: In bacteria, the translation of genetic information can begin through at least three different mechanisms. One of these mechanisms is leaderless initiation, which relies on the ability of 70S ribosomal particles to bind to AUG located at or near the 5' end of mRNAs to initiate translation. Unlike canonical translation, leaderless mRNAs lack a 5' untranslated region and a Shine-Dalgarno sequence, so the regulation of translation initiation is different for these mRNAs.
Review
Chemistry, Multidisciplinary
Florian P. Weissenboeck, Helena Schepers, Andrea Rentmeister
Summary: A major stage in gene expression is mRNA translation, and the regulation of this process is crucial for cellular protein production. Spatial and temporal control of gene expression is especially evident in polar cells and embryonic development. External bioorthogonal triggers are useful tools to dissect the complex processes and understand the underlying links, particularly in cases of malfunction. Equipping nucleic acids with light-responsive groups has been an effective approach to examine the dynamic regulation of mRNA translation in living cells. This review provides an overview of recent methods for optochemically controlling translation, with a focus on cis-acting technologies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Shuai Liu, Qiang Cheng, Tuo Wei, Xueliang Yu, Lindsay T. Johnson, Lukas Farbiak, Daniel J. Siegwart
Summary: The study successfully delivered mRNA or single-guide RNA for gene editing in vivo using combinatorially synthesized ionizable phospholipids. Optimized iPhos lipids can change shapes in endosomal acidic environments to facilitate the release of gene editing materials. When working synergistically with helper lipids, iPhos lipids can achieve targeted delivery to specific organs.
Article
Medicine, Research & Experimental
Sergio Linares-Fernandez, Julien Moreno, Elise Lambert, Perrine Mercier-Gouy, Laetitia Vachez, Bernard Verrier, Jean-Yves Exposito
Summary: Researchers developed a new mRNA structure and optimized the purification process to identify the most suitable sequences and transfection efficiency for mRNA vaccines. This technology helps to reduce the components needed for vaccines and enhance vaccine efficacy.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Review
Immunology
Andrei A. Deviatkin, Ruslan A. Simonov, Kseniya A. Trutneva, Anna A. Maznina, Anastasiia B. Soroka, Anna A. Kogan, Sofya G. Feoktistova, Elena M. Khavina, Olga N. Mityaeva, Pavel Y. Volchkov
Summary: Recently, the mRNA platform has become the method of choice in vaccine development to find new ways to fight infectious diseases. However, mRNA vaccines have the drawback of requiring special storage conditions, making them less accessible. Circular mRNAs have been proposed as a solution to this problem, as they lack the ends that are susceptible to degradation. This review summarizes the current knowledge on cap-independent translation initiation methods for circular mRNAs and discusses their potential effectiveness in developing vaccines and other biotechnological products.
Article
Biochemistry & Molecular Biology
Martyna Nowacka, Przemyslaw Latoch, Matylda A. Izert, Natalia K. Karolak, Rafal Tomecki, Michal Koper, Agnieszka Tudek, Agata L. Starosta, Maria W. Gorna
Summary: This study proposes an mRNA enrichment strategy based on the RNA-binding properties of human IFIT1, which effectively depletes rRNA while maintaining high quality RNA-seq data with coverage of the protein coding transcriptome. It is a cost-effective and versatile tool for preparing mRNA libraries for various organisms.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Inga Loedige, Artem Baranovskii, Samantha Mendonsa, Sayaka Dantsuji, Niko Popitsch, Laura Breimann, Nadja Zerna, Vsevolod Cherepanov, Miha Milek, Stefan Ameres, Marina Chekulaeva
Summary: Cells require specific shapes and subcellular compartments to perform biological functions, which is achieved through the asymmetric distribution of mRNAs. The current model of mRNA localization involves specific sequences called zipcodes, but additional mechanisms are likely involved. This study investigates the role of mRNA stability in localization and reveals that mRNA destabilization elements mediate the localization of mRNAs associated with housekeeping functions to neurites in various types of neurons.
Article
Biochemistry & Molecular Biology
Jack D. Godfrey, Daniel Hejazi, Xiaofei Du, Cenfu Wei, Eshaan Rao, Christopher M. Gomez
Summary: The HER2/neu signaling pathway is frequently mutated in human cancer and targeting this pathway is effective in treatment. However, cancer cells often develop resistance. This study shows that smaller c-terminal fragments (CTFs) of the HER2 protein, generated through internal translation, are a cause of resistance. Understanding this mechanism could lead to new therapeutic interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Jiayin Guo, Yaru Zhu, Xiaoya Ma, Guijun Shang, Bo Liu, Ke Zhang
Summary: Gene expression in eukaryotes involves transcription, mRNA synthesis, and mRNA export through the nuclear pore complex (NPC). Viral proteins can interact with host factors involved in mRNA export, leading to inhibition of host gene expression and enhanced viral mRNA export. Understanding these mechanisms can help develop antivirals to inhibit viral mRNA transport and enhance host gene expression, promoting immune responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Angelica Montiel-Davalos, Yeniffer Ayala, Greco Hernandez
Summary: Among CNS cancers, glioblastoma (GB) is the most common and aggressive type. Current treatments involve surgery, radiation, and chemotherapy, but the prognosis remains poor. Recent studies have focused on mRNA translation and its dysregulation in GB, particularly in the initiation phase. The translation machinery and ribosomal proteins have also been implicated in GB development. This review discusses the relationship between translation initiation, the translation machinery, and GB, as well as the potential of targeting the translation machinery for improved patient survival.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
M. Shelton, C. A. Anene, J. Nsengimana, W. Roberts, J. Newton-Bishop, J. R. Boyne
Summary: Exosomes play a crucial role in the crosstalk between cancer associated fibroblasts (CAFs) and cancer cells by establishing a cell-cell communication network within the tumour microenvironment through miRNA, contributing to cancer progression and metastasis.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2021)
Article
Biochemistry & Molecular Biology
Jennifer A. Miles, Fruzsina Hobor, Chi H. Trinh, James Taylor, Christian Tiede, Philip R. Rowell, Brian R. Jackson, Fatima A. Nadat, Pallavi Ramsahye, Hannah F. Kyle, Basile I. M. Wicky, Jane Clarke, Darren C. Tomlinson, Andrew J. Wilson, Thomas A. Edwards
Summary: This study utilized phage display to isolate Affimer reagents for selective recognition of BCL-2 proteins, competitive inhibition of BCL-x(L) and MCL-1 protein-protein interactions, and revealed an unprecedented mode of molecular recognition. This proof-of-concept research suggests that Affimers could be used as alternative templates for the design of selective BCL-2 family modulators and other protein-protein interaction inhibitors.
Article
Microbiology
Xiang Liu, Ali Zaid, Joseph R. Freitas, Nigel A. McMillan, Suresh Mahalingam, Adam Taylor
Summary: The study confirmed the value of the RG-rescued SARS-CoV-2 viruses in reproducing infection patterns and pathology typical of severe COVID-19 in a mouse model, providing important tools for advancing research on SARS-CoV-2 and COVID-19 therapeutics.
Article
Hematology
Jeanne F. Rivera, April J. Baral, Fatima Nadat, Grace Boyd, Rachael Smyth, Hershna Patel, Emma L. Burman, Ghadah Alameer, Sally A. Boxall, Brian R. Jackson, E. Joanna Baxter, Peter Laslo, Anthony R. Green, David G. Kent, Ann Mullally, Edwin Chen
Summary: This study identified key motifs for the oncogenic activity of CALR(de)(l52), highlighting the essential role of the zinc-binding domain in multimerization of CALR(de)(l52) and interaction with MPL. Zinc chelators showed therapeutic potential in preferentially targeting CALR(de)(l52)-mutant cells, suggesting that modulation of intracellular zinc levels could be a novel approach to inhibit the oncogenic activity of CALR(de)(l52) in MPNs treatment.
Article
Biochemistry & Molecular Biology
O. Bi, C. A. Anene, J. Nsengimana, M. Shelton, W. Roberts, J. Newton-Bishop, J. R. Boyne
Summary: The study demonstrates that SFPQ plays an important role in melanoma, driving cancer-associated cell phenotypes by interacting with coding and long non-coding RNAs. Elevated expression of SFPQ in primary melanoma tumors may serve as a prognostic biomarker for the disease.
Article
Biochemistry & Molecular Biology
Katerina Douka, Isabel Birds, Dapeng Wang, Andreas Kosteletos, Sophie Clayton, Abigail Byford, Elton J. R. Vasconcelos, Mary J. O'Connell, Jim Deuchars, Adrian Whitehouse, Julie L. Aspden
Summary: Through Poly-Ribo-Seq analysis, we identified 237 cytoplasmic lncRNAs up-regulated during early neuronal differentiation, with 45 small ORFs actively translated, 17 of which were specifically translated upon differentiation. Within these translated lncRNA-smORFs, 15 exhibit sequence conservation within Hominidea, suggesting strong selective constraint in this clade.
Article
Microbiology
Xiang Liu, Adam Taylor, Yee Suan Poo, Wern Hann Ng, Lara J. Herrero, Patrick Chun Hean Tang, Ali Zaid, Suresh Mahalingam
Summary: This study investigates the role of TIR-domain-containing adapter-inducing interferon-beta (TRIF) in the development of Ross River virus (RRV) disease. The findings suggest that TRIF plays a critical role in the immune response to RRV infection, with TRIF-deficient mice showing increased susceptibility to severe disease and high viremia. The study also reveals that TRIF affects the activation of T cells, NK cells, and B cells, as well as the production of IgG antibodies. The slower resolution of RRV disease in TRIF-deficient mice is associated with the persistence of the virus and a continuing IFN response in muscle tissue.
Article
Microbiology
Eranga Abeyratne, Ronak Reshamwala, Todd Shelper, Xiang Liu, Ali Zaid, Suresh Mahalingam, Adam Taylor
Summary: This study utilized the DigiGait system to objectively measure gait changes in mice with infectious arthritis for the first time, revealing significant differences during peak disease in RRV-infected mice. The DigiGait system provides an objective model of variations in gait dynamics in mice acutely infected with RRV.
Article
Biochemistry & Molecular Biology
Katherine L. Harper, Timothy J. Mottram, Chinedu A. Anene, Becky Foster, Molly R. Patterson, Euan McDonnell, Andrew Macdonald, David Westhead, Adrian Whitehouse
Summary: Non-coding RNA regulatory networks play a critical role in gene expression, modulating multiple cellular pathways and impacting various diseases. A novel host ncRNA regulatory network essential for KSHV lytic replication in B cells involves KSHV-mediated upregulation of host cell circHIPK3, acting as a competing endogenous RNA of miR-30c and leading to increased levels of DLL4. Dysregulation of this network during KSHV lytic replication highlights a novel mechanism of cell cycle control.
Article
Microbiology
Xiang Liu, Yee-Suan Poo, Juliana C. Alves, Roque P. Almeida, Helen Mostafavi, Patrick Chun Hean Tang, Richard Bucala, Mauro M. Teixeira, Adam Taylor, Ali Zaid, Suresh Mahalingam
Summary: CHIKV has been prevalent in Africa, Asia, and the Indian Ocean Islands for decades. There are currently no clinically approved vaccines or specific antiviral drugs targeting CHIKV. The upregulation of IL-17 detected in CHIKV disease patients and the reduced disease seen in IL-17-deficient mice suggest a correlation between IL-17 signaling pathways and CHIKV-induced arthritic inflammation. With an established role in contributing to the pathogenesis of immune-mediated diseases, such as psoriatic arthritis and rheumatoid arthritis, IL-17 signaling plays an important role in alphavirus arthritides.
Article
Microbiology
Xiang Liu, Helen Mostafavi, Wern Hann Ng, Joseph R. Freitas, Nicholas J. C. King, Ali Zaid, Adam Taylor, Suresh Mahalingam
Summary: This study characterizes the pathogenicity and immune response of the Delta variant in K18-hACE2 transgenic mice and finds that Delta causes similar clinical disease manifestations as the ancestral SARS-CoV-2 but with widespread dissemination to multiple tissues. The study also highlights distinct immune response patterns in the lungs of Delta-infected mice compared to mice infected with the ancestral strain.
Article
Biochemical Research Methods
Konstantin Roder, Amy M. Barker, Adrian Whitehouse, Samuela Pasquali
Summary: This article investigates the change in structure of an RNA regulatory molecule upon a change in the chemistry of one of its bases. The results show that a chemical modification can induce a global rearrangement of the structure, affecting regions far away from the modification site.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Virology
Kothila Tharmarajah, Arun Everest-Dass, Jelena Vider, Xiang Liu, Joseph R. Freitas, Helen Mostafavi, Jayaram Bettadapura, Mark von Itzstein, Nicholas P. West, Adam Taylor, Suresh Mahalingam, Ali Zaid
Summary: Arthritogenic alphaviruses, transmitted by mosquitoes through the skin, can cause debilitating diseases. Our understanding of how viral infection starts in the skin and disseminates to cause disease remains limited. This study reveals that intradermal arbovirus infection leads to musculoskeletal pathology, which is influenced by viral envelope glycosylation. The insights gained from this research can contribute to future investigations of skin immune responses following infection with other re-emerging arboviruses.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Gi Uk Jeong, Hyung-Jun Kwon, Wern Hann Ng, Xiang Liu, Hyun Woo Moon, Gun Young Yoon, Hye Jin Shin, In-Chul Lee, Zheng Lung Ling, Alanna G. Spiteri, Nicholas J. C. King, Adam Taylor, Ji Soo Chae, Chonsaeng Kim, Dae-Gyun Ahn, Kyun-Do Kim, Young Bae Ryu, Seong-Jun Kim, Suresh Mahalingam, Young-Chan Kwon
Summary: This study demonstrates that SARS-CoV-2 can infect the eyes and cause retinal inflammation in transgenic mice and Syrian hamster models. The virus can also spread from the lungs to the brain and eyes through neuronal pathways. These findings contribute to a better understanding of viral transmission and clinical characteristics of SARS-CoV-2 and can aid in improving COVID-19 control procedures.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
James C. Murphy, Elena M. Harrington, Sophie Schumann, Elton J. R. Vasconcelos, Timothy J. Mottram, Katherine L. Harper, Julie L. Aspden, Adrian Whitehouse
Summary: Historically, ribosomes were thought to be homogeneous machines lacking regulatory capacity, but recent discoveries have uncovered the existence of compositionally distinct, specialized ribosomes that actively regulate mRNA translation. This study focuses on the manipulation of ribosome biogenesis by KSHV to generate specialized ribosomes for efficient translation of viral mRNAs.
NATURE COMMUNICATIONS
(2023)