Article
Biochemistry & Molecular Biology
Pavel A. Sakharov, Egor A. Smolin, Dmitry N. Lyabin, Sultan C. Agalarov
Summary: The study confirms that m(6)A-modified mRNAs can be translated under conditions of cap-dependent translation inhibition, but with lower translation initiation efficiency. Additionally, the translation elongation of m(6)A-mRNAs is slower.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Ipsita Basu, Biswajit Gorai, Thyageshwar Chandran, Prabal K. Maiti, Tanweer Hussain
Summary: Accurate and high-speed scanning and selection of the correct start codon are important events in protein synthesis. Molecular dynamics simulations and energy calculations suggest that the ribosomal 48S pre-initiation complex (PIC) may reject most non-AUG codons, with initiation factor eIF1 playing a crucial role. This study provides insights into the scanning process and the involvement of initiation factors in codon-anticodon-ribosome network stability.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jinfan Wang, Byung-Sik Shin, Carlos Alvarado, Joo-Ran Kim, Jonathan Bohlen, Thomas E. Dever, Joseph D. Puglisi
Summary: Through real-time single-molecule fluorescence spectroscopy, it has been found that the eukaryotic 43S preinitiation complex engages with mRNA through a slow, ATP-dependent process and proceeds to scan rapidly and directionally along the 5' untranslated region (5' UTR). Scanning ribosomes can traverse RNA secondary structures, but hairpin structures near the start codons drive them backward in the 5' direction, requiring rescanning.
Article
Multidisciplinary Sciences
Hyun Jung Hwang, Hongseok Ha, Ban Seok Lee, Bong Heon Kim, Hyun Kyu Song, Yoon Ki Kim
Summary: LC3B has been found to play a crucial role in autophagy by binding to and degrading target mRNAs, revealing the interplay between autophagy and RNA biology.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Yi-Lan Chen, Jin-Der Wen
Summary: Initiation of protein synthesis in bacteria requires the correct recognition of the start codon on mRNA. This study investigates how the ribosome accommodates the short and degenerate information in the ribosome-binding site (RBS) to initiate translation. The researchers found that the initiation factors and the initiator tRNA play a crucial role in stabilizing the mRNA structure and promoting its unwinding by the 30S subunit. This dynamic assembly-disassembly process ensures the selection of the correct RBS. The findings provide insights into the mechanism of translation initiation in bacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Burak Cetin, Sean E. O'Leary
Summary: Studies have shown that the interaction between eIF4F and mRNA is regulated by mRNA length, cap-proximal secondary structure, eIF4A, and ATP. The activities of eIF4G and eIF4A accelerate the association rate of eIF4E with mRNA, playing a crucial role in translation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Christopher P. Lapointe, Rosslyn Grosely, Alex G. Johnson, Jinfan Wang, Israel S. Fernandez, Joseph D. Puglisi
Summary: This study investigates the novel coronavirus protein NSP1, which is proposed to inhibit protein synthesis by binding directly to the ribosome. The researchers demonstrate that NSP1 inhibits translation of both human and virus messenger RNAs by specifically binding to the small ribosomal subunit and competing with RNA segments downstream of the start codon. Furthermore, they reveal that eukaryotic translation initiation factors modulate the interaction of NSP1 with ribosomal complexes in the absence of mRNA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Jinbae Yu, Youngsik Woo, Heesun Kim, Sihyeon An, Sang Ki Park, Sung Key Jang
Summary: FMRP is a multifunctional protein encoded by the FMR1 gene, and its deficiency is associated with fragile X syndrome. We discovered that FMRP controls neuronal development by enhancing the translation of 4EBP2, a key downstream regulator. This finding contributes to our understanding of the pathology of fragile X syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Multidisciplinary
Pei Huang, Hongzhang Deng, Changrong Wang, Yongfeng Zhou, Xiaoyuan Chen
Summary: Messenger RNA (mRNA)-based therapy is a powerful, safe, and rapidly scalable therapeutic approach. In this review, therapeutic applications of mRNA are introduced, common types of mRNA cargos and delivery systems are summarized, and strategies to enhance nanotechnology-mediated mRNA delivery efficiency during the cellular trafficking process are highlighted.
ADVANCED MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Nikita Biziaev, Elizaveta Sokolova, Dmitry V. Yanvarev, Ilya Yu Toropygin, Alexey Shuvalov, Tatiana Egorova, Elena Alkalaeva
Summary: The nucleotide context surrounding stop codons significantly affects the efficiency of translation termination. This study found that in the absence of eukaryotic release factors (eRFs), readthrough of stop codons occurs in a 3' nucleotide context-dependent manner. The type of stop codon and the sequence of the 3' nucleotides are the main factors determining readthrough efficiency.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Developmental Biology
Anupama Rao, Baken Lyu, Ishrat Jahan, Anna Lubertozzi, Gao Zhou, Frank Tedeschi, Eckhard Jankowsky, Junsu Kang, Bryan Carstens, Kenneth D. Poss, Kedryn Baskin, Joseph Aaron Goldman
Summary: The eIF4E family of translation initiation factors is important for heart development and regeneration, particularly the Eif4e1c family. Deletion of Eif4e1c in zebrafish causes growth deficits and impaired proliferative responses to cardiac injury. Ribosome profiling also reveals changes in translation efficiency of genes known to regulate cardiomyocyte proliferation.
Article
Biochemistry & Molecular Biology
Paul Powell, Usha Bhardwaj, Dixie Goss
Summary: This study identifies secondary structures that selectively interact with eIF3 and explores its role in translation initiation of BYDV. The findings propose a new model for BYDV translation initiation and expand the known functionality of eIF3.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Danielle M. Garshott, Heeseon An, Elayanambi Sundaramoorthy, Marilyn Leonard, Alison Vicary, J. Wade Harper, Eric J. Bennett
Summary: Post-translational modification of ribosomal proteins plays a crucial role in regulating protein biogenesis, with specific ubiquitylation events on 40S ribosomal proteins identified. The study also uncovers the regulatory mechanisms of the ubiquitylation of uS3 and uS5 proteins, as well as the initiation RQC pathway (iRQC) that modulates translation activity on 40S ribosomes during translation initiation.
Article
Multidisciplinary Sciences
Irmgard U. Haussmann, Yanying Wu, Mohanakarthik P. Nallasivan, Nathan Archer, Zsuzsanna Bodi, Daniel Hebenstreit, Scott Waddell, Rupert Fray, Matthias Soller
Summary: Two cap methyltransferases in Drosophila can methylate the ribose of the first nucleotide in mRNA, contributing to reward learning and localization of untranslated mRNAs to synapses.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Leandro Fernandez-Garcia, Jenniffer Angulo, Hade Ramos, Aldo Barrera, Karla Pino, Jorge Vera-Otarola, Marcelo Lopez-Lastra
Summary: The DENV IRES enables viral protein synthesis under conditions that suppress canonical translation initiation, with resistance to eIF4G cleavage and enhanced activity in HEK 293T cells expressing Human rhinovirus 2A protease. This study characterizes the mechanism dependent on an internal ribosome entry site (IRES) for DENV mRNA translation initiation both in vitro and in cells.
JOURNAL OF VIROLOGY
(2021)
Letter
Cell Biology
Hui Ming, Qianfeng Wang, Yuwen Zhang, Luzhang Ji, Lu Cheng, Xiangru Huo, Zixiang Yan, Zhexiao Liu, Yongjun Dang, Bo Wen
Article
Chemistry, Medicinal
Nannan Sun, Qiong Xie, Yongjun Dang, Yonghui Wang
Summary: ROR gamma t is a potential drug target for autoimmune diseases with complex relationship between agonist lock and inverse agonism. Different inverse agonists adopt different interference mechanisms.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Richard Lewis, H. Carlo Maurer, Nikita Singh, Irene Gonzalez-Menendez, Matthias Wirth, Markus Schick, Le Zhang, Konstandina Isaakidis, Anna Katharina Scherger, Veronika Schulze, Junyan Lu, Thorsten Zenz, Katja Steiger, Roland Rad, Leticia Quintanilla-Martinez, Marion Espeli, Karl Balabanian, Ulrich Keller, Stefan Habringer
Summary: The study reveals that hyperactivation of CXCR4 is identified as a co-driver of an aggressive lymphoma phenotype.
Article
Oncology
Friederike Herbst, Tonio J. L. Lang, Elias S. P. Eckert, Peer Wunsche, Alexander A. Wurm, Tim Kindinger, Karin Laaber, Shayda Hemmati, Agnes Hotz-Wagenblatt, Oksana Zavidij, Anna Paruzynski, Junyan Lu, Christof von Kalle, Thorsten Zenz, Christoph Klein, Manfred Schmidt, Claudia R. Ball, Hanno Glimm
Summary: The EVL/MIR342 gene locus is identified as a hotspot for therapeutic vector insertions in human hematopoietic stem and progenitor cells, with EVL and its intronic miRNA-342 regulating hematopoiesis by promoting lymphopoiesis and myeloid colony formation respectively. MiR-342 counteracts its host gene EVL, targeting lymphoid signaling pathways and reducing pre-B-cell output, highlighting a balance between the two factors in determining hematopoietic cell fate.
Letter
Oncology
Marco M. Buhler, Junyan Lu, Sebastian Scheinost, Ferran Nadeu, Damien Roos-Weil, Manfred Hensel, Tharshika Thavayogarajah, Holger Moch, Markus G. Manz, Eugenia Haralambieva, Ewerton Marques Maggio, Silvia Bea, Eva Gine, Elias Campo, Olivier A. Bernard, Wolfgang Huber, Thorsten Zenz
Article
Multidisciplinary Sciences
Haikun Song, Cen Wang, Chenggang Zhu, Ziying Wang, Huiya Yang, Peng Wu, Xiaotian Cui, Juan Botas, Yongjun Dang, Yu Ding, Yiyan Fei, Boxun Lu
Summary: Chemical binders targeting mutant huntingtin protein (mHTT) have the potential to inhibit Huntington's disease (HD) by destabilizing the protein through enhancing its polyubiquitination.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Peter-Martin Bruch, Holly A. R. Giles, Carolin Kolb, Sophie A. Herbst, Tina Becirovic, Tobias Roider, Junyan Lu, Sebastian Scheinost, Lena Wagner, Jennifer Huellein, Ivan Berest, Mark Kriegsmann, Katharina Kriegsmann, Christiane Zgorzelski, Peter Dreger, Judith B. Zaugg, Carsten Mueller-Tidow, Thorsten Zenz, Wolfgang Huber, Sascha Dietrich
Summary: The tumor microenvironment and genetic alterations play a collective role in influencing the efficacy of cancer drugs. This study investigated the impact of microenvironmental stimuli on drug response in chronic lymphocytic leukemia (CLL) patients and identified distinct subgroups with different clinical outcomes. The researchers also found that trisomy 12 samples exhibited amplified response to multiple microenvironmental stimuli and had a unique epigenetic signature. Additionally, interleukin 4 (IL4) and Toll-like receptor (TLR) signaling were identified as strong contributors to drug resistance. The findings highlight the importance of considering both microenvironmental factors and genetic alterations in cancer treatment.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Hematology
Pau Abrisqueta, Daniel Medina, Guillermo Villacampa, Junyan Lu, Miguel Alcoceba, Julia Carabia, Joan Boix, Barbara Tazon-Vega, Gloria Iacoboni, Sabela Bobillo, Ana Marin-Niebla, Marcos Gonzalez, Thorsten Zenz, Marta Crespo, Francesc Bosch
Summary: This study developed a gene expression-based prediction model for early progression in chronic lymphocytic leukemia (CLL). By analyzing 200 genes related to microenvironment signaling, the CLL15 assay was found to be significantly associated with time to first treatment (TtFT) in both the training and validation cohorts. The CLL15 score demonstrated improved prognostic capacity compared to other indicators, such as IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL.
Article
Multidisciplinary Sciences
Allison Mitchell, Ling Wu, C. James Block, Mu Zhang, Justin Hackett, Douglas B. Craig, Wei Chen, Yongzhong Zhao, Bin Zhang, Yongjun Dang, Xiaohong Zhang, Shengping Zhang, Chuangui Wang, Heather Gibson, Lori A. Pile, Benjamin Kidder, Larry Matherly, Zhe Yang, Yali Dou, Guojun Wu
Summary: The study reveals that FOXQ1 recruits the MLL/KMT2 histone methyltransferase complex as a transcriptional coactivator to initiate EMT in breast cancer. Disruption of FOXQ1-RbBP5 interaction or pharmacologic targeting of KMT2/MLL recruitment inhibits FOXQ1-dependent gene expression, EMT, and in vivo tumor progression. Targeting the FOXQ1-MLL epigenetic axis could be a promising strategy against metastatic progression in triple-negative breast cancer.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Sophie A. Herbst, Mattias Vesterlund, Alexander J. Helmboldt, Rozbeh Jafari, Ioannis Siavelis, Matthias Stahl, Eva C. Schitter, Nora Liebers, Berit J. Brinkmann, Felix Czernilofsky, Tobias Roider, Peter-Martin Bruch, Murat Iskar, Adam Kittai, Ying Huang, Junyan Lu, Sarah Richter, Georgios Mermelekas, Husen Muhammad Umer, Mareike Knoll, Carolin Kolb, Angela Lenze, Xiaofang Cao, Cecilia Osterholm, Linus Wahnschaffe, Carmen Herling, Sebastian Scheinost, Matthias Ganzinger, Larry Mansouri, Katharina Kriegsmann, Mark Kriegsmann, Simon Anders, Marc Zapatka, Giovanni Del Poeta, Antonella Zucchetto, Riccardo Bomben, Valter Gattei, Peter Dreger, Jennifer Woyach, Marco Herling, Carsten Muller-Tidow, Richard Rosenquist, Stephan Stilgenbauer, Thorsten Zenz, Wolfgang Huber, Eugen Tausch, Janne Lehtioe, Sascha Dietrich
Summary: Cancer heterogeneity at the proteome level can explain therapy response and prognosis differences. This study focuses on chronic lymphocytic leukemia (CLL) and identifies a new subgroup of patients, ASB-CLL, with poor prognosis. Proteomics has the potential to improve cancer patient stratification beyond genetic and transcriptomic profiling.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Maurizio Mangolini, Alba Maiques-Diaz, Stella Charalampopoulou, Elena Gerhard-Hartmann, Johannes Bloehdorn, Andrew Moore, Giorgia Giachetti, Junyan Lu, Valar Nila Roamio Franklin, Chandra Sekkar Reddy Chilamakuri, Ilias Moutsopoulos, Andreas Rosenwald, Stephan Stilgenbauer, Thorsten Zenz, Irina Mohorianu, Clive D'Santos, Silvia Deaglio, Daniel J. Hodson, Jose Martin-Subero, Ingo Ringshausen
Summary: Mutations in NOTCH1 and NOTCH2 contribute to immune escape of malignant B cells by up-regulating PD-L1 and silencing the HLA-II locus, possibly affecting the effectiveness of immune therapies.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Alina Batzilla, Junyan Lu, Jarno Kivioja, Kerstin Putzker, Joe Lewis, Thorsten Zenz, Wolfgang Huber
Summary: The development of cancer therapies can be improved by discovering tumor-specific molecular dependencies. A mathematical model, called DepInfeR, was developed to computationally infer specific molecular dependencies of individual cancers using protein-drug affinity data. This method accurately identified known protein kinase dependencies and uncovered new subgroup-specific dependencies.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Cell Biology
Veronika Ecker, Lisa Brandmeier, Martina Stumpf, Piero Giansanti, Aida Varela Moreira, Lisa Pfeuffer, Marcel H. . A. M. Fens, Junyan Lu, Bernhard Kuster, Thomas Engleitner, Simon Heidegger, Roland Rad, Ingo Ringshausen, Thorsten Zenz, Clemens-Martin Wendtner, Markus Muschen, Julia Jellusova, Jurgen Ruland, Maike Buchner
Summary: Inhibition of the phosphatases DUSP1 and DUSP6 reduces cell survival and induces cell death in chronic lymphocytic leukemia. Transient inhibition of DUSP1/6 shows promise as a treatment concept for drug-resistant CLL.
Article
Oncology
Nora Liebers, Peter-Martin Bruch, Tobias Terzer, Miguel Hernandez-Hernandez, Nagarajan Paramasivam, Donnacha Fitzgerald, Heidi Altmann, Tobias Roider, Carolin Kolb, Mareike Knoll, Angela Lenze, Uwe Platzbecker, Christoph Roellig, Claudia Baldus, Hubert Serve, Martin Bornhaeuser, Daniel Huebschmann, Carsten Mueller-Tidow, Friedrich Stoelzel, Wolfgang Huber, Axel Benner, Thorsten Zenz, Junyan Lu, Sascha Dietrich
Summary: This study conducted a prospective non-interventional trial to investigate the potential of ex vivo drug response profiling for treatment guidance in hematologic malignancies. The results showed that ex vivo drug response profiling has the potential to predict chemotherapy response and improve risk stratification.
Article
Oncology
Junyan Lu, Ester Cannizzaro, Fabienne Meier-Abt, Sebastian Scheinost, Peter-Martin Bruch, Holly A. R. Giles, Almut Lutge, Jennifer Huellein, Lena Wagner, Brian Giacopelli, Ferran Nadeu, Julio Delgado, Elias Campo, Maurizio Mangolini, Ingo Ringshausen, Martin Bottcher, Dimitrios Mougiakakos, Andrea Jacobs, Bernd Bodenmiller, Sascha Dietrich, Christopher C. Oakes, Thorsten Zenz, Wolfgang Huber
Summary: Huber and colleagues identified a proliferative drive axis involving mTOR, MYC, and OXPHOS metabolic activity in CLL, which is associated with disease heterogeneity and outcome. Their multi-omic analysis revealed a biological axis of heterogeneity strongly linked to clinical behavior and orthogonal to known biomarkers. The CLL proliferative drive axis was validated in multiple cohorts and is a key determinant of disease outcome.