Article
Biochemistry & Molecular Biology
Tom Dendooven, Elisabeth Sonnleitner, Udo Blaesi, Ben F. Luisi
Summary: The bacterial RNA chaperone Hfq and its partner protein Crc form higher order assemblies on control regions of different P. aeruginosa target mRNAs. These assemblies have mRNA-specific quaternary architectures due to the combination of multivalent protein-protein interfaces and recognition of patterns in the RNA sequence. The structural polymorphism of these ribonucleoprotein assemblies enables selective translational repression of many different target mRNAs.
Article
Biochemical Research Methods
Hideyuki Nakanishi, Hirohide Saito, Keiji Itaka
Summary: Synthetic mRNA is a valuable tool for medical applications, as it allows for transgene expression without the need for nuclear import and the risk of insertional mutagenesis. In this study, a protein-responsive translational regulation system was developed using Caliciviral VPg-based translational activator, inteins, and target protein-binding nanobodies. This system enables both activation and repression of translation in a target protein-dependent manner, with the ability to easily change the target protein. This versatile design offers a safe approach to target protein-responsive translational regulation therapeutics.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Wujing Dai, Han Qu, Jack Zhang, Angkana Thongkum, Thai Nho Dinh, Kyle Kappeler, Qin M. Chen
Summary: Oxidative stress triggers de novo translation of Nrf2 protein in cells, with FUBP1 playing a regulatory role. FUBP1 promotes the attachment of 40S ribosomal subunit to Nrf2 mRNA and formation of 43S pre-initiation complex for translation initiation of Nrf2 protein under oxidative stress.
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
Oncology
Morgane Le Bras, Noah Gorelick, Sylvain Pautet, Betty Tyler, Stephane Manenti, Nicolas Skuli, Stefania Millevoi, Anne Cammas
Summary: This study investigates the molecular mechanisms underlying protein synthesis deregulation in glioblastoma (GBM) and its impact on tumor progression and resistance to therapy. The results reveal the crucial role of RNA-binding proteins hnRNP H/F in controlling protein synthesis in GBM through overlapping mechanisms. Furthermore, hnRNP H/F are shown to potentiate cellular processes that contribute to the aggressive and resistant phenotype of GBMs, indicating their potential as therapeutic targets.
Article
Biochemical Research Methods
Michael T. A. Nguyen, Georgios Pothoulakis, Ebbe S. Andersen
Summary: This study presents an approach for regulating translation in Escherichia coli using the MS2 and PP7 aptamer and coat-protein pairs. It demonstrates that RNA origami scaffolds can activate protein expression, and also shows the regulation of multiple proteins using a single MS2 coat protein fusion.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Cell Biology
Qiyan Yin, Min Zheng, Qianmei Luo, Dewei Jiang, Huifeng Zhang, Ceshi Chen
Summary: Y box binding protein 1 (YB-1) is a versatile protein with important roles in gene transcription, RNA splicing, DNA damage repair, cell cycle progression, and immunity. Accumulating evidence suggests that YB-1 promotes tumor progression in various types of cancers and may serve as a potential therapeutic target.
Review
Oncology
Douglas S. Micalizzi, Richard Y. Ebright, Daniel A. Haber, Shyamala Maheswaran
Summary: The deregulation of mRNA translation plays a crucial role in cancer cell spread and metastasis by influencing cellular states and responses to external stresses. This review focuses on the importance of altered translation in driving phenotypic changes and responses in metastatic progression, highlighting potential therapeutic opportunities to target metastatic tumor cells.
Article
Cell Biology
Asra Abukar, Martin Wipplinger, Ananya Hariharan, Suna Sun, Manuel Ronner, Marika Sculco, Agata Okonska, Jelena Kresoja-Rakic, Hubert Rehrauer, Weihong Qi, Victor W. van Beusechem, Emanuela Felley-Bosco
Summary: The study reveals that RBM8A is highly expressed in mesothelioma, and its mRNA editing can stabilize protein expression levels. ADAR-dependent editing contributes to maintaining elevated RBM8A protein levels in mesothelioma by counteracting MSI2-driven downregulation.
Article
Biochemistry & Molecular Biology
Katarzyna Taylor, Agnieszka Piasecka, Arkadiusz Kajdasz, Aleksandra Brzek, Micaela Polay Espinoza, Cyril F. Bourgeois, Artur Jankowski, Malgorzata Borowiak, Katarzyna D. Raczynska, Lukasz J. Sznajder, Krzysztof Sobczak
Summary: This study aims to elucidate the mechanism of muscleblind-like splicing regulators (MBNLs) in alternative splicing (AS) processes. The findings indicate that DEAD-box (DDX) RNA helicases DDX5 and DDX17 play an important role in MBNL-dependent AS regulation. The helicases modulate MBNL splicing activity through changes in the ratio of MBNL splicing isoforms and accessibility of MBNL-binding sites. These findings contribute to a deeper understanding of the interdependencies between RNA-binding proteins and their implications in developmental homeostasis and pathological states.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ari Dwijayanti, Marko Storch, Guy-Bart Stan, Geoff S. Baldwin
Summary: This article introduces a modular artificial RNA interference method called mARi, which enables robust, portable and multiplexed post-transcriptional regulation in Escherichia coli. The study demonstrates the independence and extensibility of mARi and provides new insights into RNA-based regulation design in E. coli.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Immunology
Derrick Watkins, Dev Arya
Summary: Hfq is essential for the interaction between sRNA and mRNA in many Gram-negative bacteria. However, in Gram-positive bacteria, sRNA can bind mRNA targets independently of Hfq. Although the global structure of Hfq is conserved, variations in the binding surfaces of Hfq result in the recognition of different RNA sequences.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexandra Schilder, Boris Goerke
Summary: In enteric bacteria, small RNAs (sRNAs) such as MicC stimulate target RNA decay using RNase E. The interaction between the sRNA 5' monophosphate (5 ' P) and RNase E activates cleavage of the target. However, experimental evidence supporting this model is limited. To address this, researchers developed a genetic tool to generate controllable 5' monophosphorylated sRNAs. The results showed that while the 5' phosphorylation state determines stability of naturally triphosphorylated sRNAs, it does not play a major role in target RNA destabilization in vivo. Additionally, the C-terminal half of RNase E is crucial for MicC-mediated decay, suggesting the mandatory interaction with Hfq.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Anatomy & Morphology
Federico Cremisi, Robert Vignali
Summary: Differentiation of specific neuronal types in the nervous system involves a complex series of gene regulation events. In the mammalian neocortex, key transcription factors play a crucial role in allocating neurons to different cortical layers and giving them specific properties. Recent evidence suggests that micro-RNAs and RNA-binding proteins are important for the time-controlled regulation of gene products during cortical development, and their effects may contribute to the diversity of cortical cell types within mammals.
FRONTIERS IN NEUROANATOMY
(2023)
Article
Biochemistry & Molecular Biology
Xi Yang, Weiguo Dong, Wenqing Ren, Qiuxia Zhao, Feijie Wu, Yuke He
Summary: In plants, HYL1, a core component of the miRNA processing machinery, regulates miRNA-mediated mRNA translation in the cytoplasm by monitoring the distribution of AGO1 onto polysomes, binding to the mRNAs of target genes, and repressing their translation. This study uncovered another function of HYL1 and provides insight into the mechanism of plant gene regulation.
Review
Microbiology
Bjarne Hove-Jensen, Ditlev E. Brodersen, M. Cemre Manav
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2019)
Article
Biochemistry & Molecular Biology
Ragnhild Bager Skjerning, Meriem Senissar, Kristoffer S. Winther, Kenn Gerdes, Ditlev E. Brodersen
MOLECULAR MICROBIOLOGY
(2019)
Article
Multidisciplinary Sciences
Kasper U. Kjeldsen, Lars Schreiber, Casper A. Thorup, Thomas Boesen, Jesper T. Bjerg, Tingting Yang, Morten S. Dueholm, Steffen Larsen, Nils Risgaard-Petersen, Marta Nierychlo, Markus Schmid, Andreas Boggild, Jack van de Vossenberg, Jeanine S. Geelhoed, Filip J. R. Meysman, Michael Wagner, Per H. Nielsen, Lars Peter Nielsen, Andreas Schramm
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2019)
Article
Biochemistry & Molecular Biology
Bente K. Hansen, Camilla K. Larsen, Jakob T. Nielsen, Esben B. Svenningsen, Lan B. Van, Kristian M. Jacobsen, Morten Bjerring, Rasmus K. Flygaard, Lasse B. Jenner, Lene N. Nejsum, Ditlev E. Brodersen, Frans A. A. Mulder, Thomas Torring, Thomas B. Poulsen
Article
Endocrinology & Metabolism
Martin Overgaard, Dorte Glintborg, Henrik Thybo Christesen, Tina Kold Jensen, Marianne Skovsager Andersen
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Marie B. Bertelsen, Meriem Senissar, Maja H. Nielsen, Francesco Bisiak, Marta Cunha, Ashley L. Molinaro, Dayle A. Daines, Ditlev E. Brodersen
Summary: The study presents the structure of the intact H. influenzae VapXD complex, showing an unusual 2:1 TA molecular stoichiometry. The VapX antitoxin consists of a domain that can dock into a cavity on the toxin dimer, while the VapD toxin can adapt to interacting with an asymmetrical antitoxin.
Article
Multidisciplinary Sciences
M. Cemre Manav, Lan B. Van, Jinzhong Lin, Anders Fuglsang, Xu Peng, Ditlev E. Brodersen
NATURE COMMUNICATIONS
(2020)
Review
Microbiology
Gert Bange, Ditlev E. Brodersen, Anastasia Liuzzi, Wieland Steinchen
Summary: Under stressful growth conditions and nutrient starvation, bacteria adapt by synthesizing signaling molecules that profoundly reprogram cellular physiology, with (p)ppGpp playing a key role in this process. The synthesis and hydrolysis of this signaling molecule are carried out by specific enzymes, directly impacting intracellular effectors. Studies have revealed both common features and differences in the effects of (p)ppGpp on gram-negative and gram-positive bacteria.
ANNUAL REVIEW OF MICROBIOLOGY, VOL 75, 2021
(2021)
News Item
Biochemistry & Molecular Biology
Anastasia Liuzzi, Ditlev E. Brodersen
Summary: Studies show that prokaryotic genomes contain highly similar toxin-antitoxin modules, which need to be balanced between protection and diversification. Research on paralogous modules now reveals how evolution secures insulation between related systems without compromising toxin inhibition.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Casper Thorup, Caitlin Petro, Andreas Boggild, Tine Sneibjerg Ebsen, Signe Brokjaer, Lars Peter Nielsen, Andreas Schramm, Jesper Jensen Bjerg
Summary: This study introduces a method for establishing a stable single-strain cable bacterium culture and successfully isolates a new strain, GS, belonging to Ca. Electronema. The single-strain culture is valuable for physiological and omics-based research.
SYSTEMATIC AND APPLIED MICROBIOLOGY
(2021)
Article
Microbiology
Kenn Gerdes, Rene Baerentsen, Ditlev E. Brodersen
Summary: Toxin-antitoxin modules play vital roles in bacterial drug tolerance and persistence. A comprehensive phylogenetic analysis of Hip kinases revealed seven new kinase families, expanding the diversity in bacterial and archaeal genomes. This study opens up new avenues for the experimental analysis of the superfamily of Hip kinases.
Meeting Abstract
Biochemistry & Molecular Biology
Ditlev E. Brodersen, Soren K. Amstrup, Nicholas E. Sofos, Jesper Karlsen, Ragnhild Skjerning, Thomas Boesen, Jan J. Enghild, Bjarne H. Jensen
Article
Biochemistry & Molecular Biology
Francesco Bisiak, Adriana Chrenkova, Sheng-Da Zhang, Jannik N. Pedersen, Daniel E. Otzen, Yong E. Zhang, Ditlev E. Brodersen
Summary: The bacterial stringent response involves metabolic reprogramming to increase long-term survivability under stress conditions. The production and degradation of alarmones, modified nucleotides that affect cellular pathways, depend on enzymes from the RelA/SpoT family. Crystal structures of small alarmone hydrolases (SAHs) from two bacteria show that structural differences in substrate access and dimer conformations regulate their activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Nanoscience & Nanotechnology
Ewan K. S. McRae, Helena Ostergaard Rasmussen, Jianfang Liu, Andreas Boggild, Michael T. A. Nguyen, Nestor Sampedro Vallina, Thomas Boesen, Jan Skov Pedersen, Gang Ren, Cody Geary, Ebbe Sloth Andersen
Summary: RNA origami is a method for designing RNA nanostructures that can self-assemble through co-transcriptional folding. This study uses cryogenic electron microscopy to determine the structure of RNA origami sheets and bundles, revealing structural parameters and folding principles. The study also combines sheets and bundles to construct a multidomain satellite shape and characterizes its flexibility using cryo-electron tomography.
NATURE NANOTECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Soren K. Amstrup, Sui Ching Ong, Nicholas Sofos, Jesper L. Karlsen, Ragnhild B. Skjerning, Thomas Boesen, Jan J. Enghild, Bjarne Hove-Jensen, Ditlev E. Brodersen
Summary: Using cryogenic electron microscopy, researchers discovered that PhnJ mediates the binding of the ATP-binding cassette proteins PhnK and PhnL to the core complex, and ATP hydrolysis leads to structural rearrangement and opening of the complex. This study sheds light on the breakdown of phosphonate in bacteria and provides insights into the mechanism of the large carbon-phosphorus lyase enzyme.
NATURE COMMUNICATIONS
(2023)