Article
Biochemistry & Molecular Biology
Nova Fong, Ryan M. Sheridan, Srinivas Ramachandran, David L. Bentley
Summary: The pause-release model of transcription proposes that RNA Pol II pauses around 40-100 bases from the start site, followed by release into productive elongation. This pause release is facilitated by the PTEFb phosphorylation of the RNA Pol II elongation factor, Spt5. Researchers mapped paused polymerases using eNET-seq and found that pausing frequently occurs within gene regions even when PTEFb is inhibited. The fraction of paused polymerases gradually declines over several kb, contrary to the predicted abrupt decline for a discrete pause-release event. Spt5 depletion extends pausing zones and promotes the maturation of elongation complexes to a low-pausing state. Mutations in the CTR1 domain diminish pausing throughout genes when they mimic phosphorylation, while phosphorylation-preventing mutations in the Spt5 RNA-binding domain strengthen pausing. Hence, different Spt5 phospho-isoforms regulate the balance between pausing and elongation.
Article
Physics, Multidisciplinary
Purba Chatterjee, Nigel Goldenfeld, Sangjin Kim
Summary: Recent experiments have shown that mechanical stress associated with transcription can lead to a transition in RNA polymerase group dynamics from cooperative to antagonistic upon promoter repression. A continuum deterministic model for transcription under torsion was developed to elucidate the mechanism behind this transition, successfully reproducing experimental findings and shedding light on the interplay of mechanical and biological factors in the collective dynamics of molecular machines involved in gene expression.
PHYSICAL REVIEW LETTERS
(2021)
Article
Chemistry, Physical
Congmin Yuan, Eshani C. Goonetilleke, Ilona Christy Unarta, Xuhui Huang
Summary: The ongoing pandemic caused by SARS-CoV-2 highlights the need for effective therapeutics. Inhibition of SARS-CoV-2 RdRp by nucleotide analogs offers a promising antiviral strategy. Research on 2'-modified nucleotides shows varying inhibitory effects on SARS-CoV-2 RdRp, which could potentially aid in the rational design of antiviral agents.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Kristina Zumer, Kerstin C. Maier, Lucas Farnung, Martin G. Jaeger, Petra Rus, Georg Winter, Patrick Cramer
Summary: Transcription by RNA polymerase II requires elongation factors PAF, RTF1, and SPT6. Depletion of RTF1 reduces RNA Pol II velocity, while depletion of SPT6 impairs RNA Pol II progression through nucleosomes. These findings suggest distinct roles of elongation factors in regulating RNA Pol II activity.
Article
Biochemistry & Molecular Biology
Kai Zhou, Songkuan Zhuang, Fulong Liu, Yanheng Chen, You Li, Shihui Wang, Yuxuan Li, Huixin Wen, Xiaohua Lin, Jie Wang, Yue Huang, Cailing He, Nan Xu, Zongshu Li, Lang Xu, Zixuan Zhang, Lin-Feng Chen, Ruichuan Chen, Min Liu
Summary: P-TEFb modulates RNA polymerase II elongation through interaction with Brd4 and SEC. This study uncovers a novel mechanism for the reassembly of Cdk9 and CycT1 monomers on chromatin to form active P-TEFb.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Tom Landgraf, Albrecht Eduard Voelklein, Boris Fuertig, Harald Schwalbe
Summary: Riboswitches are gene regulatory elements located in untranslated mRNA regions that bind inducer molecules with high affinity and specificity. Understanding the interaction between cyclic-di-nucleotides and riboswitches provides insights into gene regulation mechanisms. Experimental and computational studies allow us to predict riboswitch gene regulation and its dependence on transcription speed, pausing, and ligand concentration.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Benjamin M. Spector, Mrutyunjaya Parida, Ming Li, Christopher B. Ball, Jeffery L. Meier, Donal S. Luse, David H. Price
Summary: Interactions between the RNA polymerase II preinitiation complex (PIC) and paused early elongation complexes with the +1 nucleosome are functionally important. However, there are differences in these interactions between cellular chromatin and the human cytomegalovirus (HCMV) genome. Host PICs and paused Pol II complexes frequently interact with the +1 nucleosome, while viral transcription complexes have limited nucleosomal interactions.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Lauren L. Porter, Allen K. Kim, Swechha Rimal, Loren L. Looger, Ananya Majumdar, Brett D. Mensh, Mary R. Starich, Marie-Paule Strub
Summary: This study predicts fold switching in the NusG transcription factor family using a comparative sequence-based approach and confirms the predictions through experiments. It reveals that fold switching may be a widespread mechanism of transcriptional regulation in all kingdoms of life.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Fiorella Ghisays, Aitor Garzia, Hexiao Wang, Claudia Canasto-Chibuque, Marcel Hohl, Sharon A. Savage, Thomas Tuschl, John H. J. Petrini
Summary: Telomere repeat containing RNAs (TERRAs) are a family of long non-coding RNAs transcribed from the subtelomeric regions of eukaryotic chromosomes. The helicase RTEL1 influences the abundance and localization of TERRA in human cells, with its preferred binding to G-quadruplex structures in TERRA. The regulation of TERRA by RTEL1 is crucial for cell viability and its loss may contribute to disease phenotypes in patients with RTEL1 mutations.
NATURE COMMUNICATIONS
(2021)
Article
Nanoscience & Nanotechnology
Mathias Centola, Erik Poppleton, Sujay Ray, Martin Centola, Robb Welty, Julian Valero, Nils G. Walter, Petr Sulc, Michael Famulok
Summary: Molecular engineering aims to design nanoassemblies for complex tasks, but efficient chemical-fuel-driven nanoscale driver-follower systems have not been realized. In this study, a DNA nanomachine driven by the chemical energy of DNA-templated RNA-transcription-consuming nucleoside triphosphates was developed, generating rhythmic pulsating motion and successfully coupling with a passive follower.
NATURE NANOTECHNOLOGY
(2023)
Article
Virology
Qianqian Xie, Jigui Wang, Jun Su, Chenchen Gu, Jing Wu, Jun Xiao, Weiquan Liu
Summary: The NS1 protein of mink enteritis virus (MEV) is a multifunctional protein with nuclease, helicase, and transactivation activities. Mutations in potential amino acids critical for DNA binding in the MEV NS1 resulted in a termination of viral production. Different mutations affected the transactivation activity and integrity of the NS1 protein as well as its ability to interact with SP1 and bind to the DNA-binding sites in the P38 promoter, leading to transcriptional repression.
Article
Chemistry, Multidisciplinary
Yun Lu, Zhichao Yu, Xinan Yang, Jingjing Dai, Peihui Shan, Xianhao Feng, Zhu Tao, Carl Redshaw, Xin Xiao
Summary: The binding interactions between 4-aminopyridine (4-AP) and a series of cucurbit[n]urils (Q[5], Q[6], TMeQ[6], Q[7], Q[8]) were investigated using various techniques. The results showed that only the Q[5]@4-AP complex exhibited exo binding while the other hosts formed different types of complexes. X-ray crystallography provided detailed information on the binding modes of Q[n]s with 4-AP. The study revealed the importance of cavity size in determining the stability of the complexes. Overall, the research provides valuable insights into the binding properties of cucurbit[n]urils with 4-AP. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.
CHINESE CHEMICAL LETTERS
(2023)
Article
Entomology
Yuling Peng, Kangkang Niu, Guoxing Yu, Mingxi Zheng, Qiulan Wei, Qisheng Song, Qili Feng
Summary: It has been found that the non-B form DNA structures, like G-quadruplex (G4) and i-motif, are involved in important biological processes. This study investigated the binding mechanism between the silkworm transcription factor BmLARK and BmPOUM2G4, identifying key amino acid residues and domains involved in the interaction. The results suggest that the RRM domains, especially the RNP1 and RNP2 motifs, play crucial roles in both RNA recognition and G4 structure binding.
Article
Multidisciplinary Sciences
Marten A. Hoeksema, Zeyang Shen, Inge R. Holtman, An Zheng, Nathan J. Spann, Isidoro Cobo, Melissa Gymrek, Christopher K. Glass
Summary: The study evaluated how genetic variations in five inbred strains of mice influence macrophage responses to interleukin-4 (IL-4), revealing strain-specific patterns in gene expression induced by IL-4. Through deep learning and motif mutation analysis, the dominant combinations of transcription factors driving IL-4 enhancer activation were identified in macrophages from each strain.
Article
Plant Sciences
Yu-Hsuan Cheng, Mickael Durand, Virginie Brehaut, Fu-Chiun Hsu, Zsolt Kelemen, Yves Texier, Anne Krapp, Yi-Fang Tsay
Summary: NLP6 and NLP7 act as activators in nitrate signaling and repressors under ammonium conditions to regulate different genes. Nuclear localization and nucleocytosolic shuttling of NLP6 and NLP7 are independent of each other. NLP6 and NLP7 play a more dominant role in the response to high nitrate.
Article
Multidisciplinary Sciences
Philipp Konrad Zuber, Kristian Schweimer, Paul Roesch, Irina Artsimovitch, Stefan H. Knauer
NATURE COMMUNICATIONS
(2019)
Article
Multidisciplinary Sciences
Benjamin R. Dudenhoeffer, Jan Borggraefe, Kristian Schweimer, Stefan H. Knauer
SCIENTIFIC REPORTS
(2020)
Article
Immunology
Frederike A. Hartl, Esmeralda Beck-Garcia, Nadine M. Woessner, Lea J. Flachsmann, Rubi M-H Velasco Cardenas, Simon M. Brandl, Sanaz Taromi, Gina J. Fiala, Anna Morath, Pankaj Mishra, O. Sascha Yousefi, Julia Zimmermann, Nico Hoefflin, Maja Koehn, Birgitta M. Woehrl, Robert Zeiser, Kristian Schweimer, Stefan Guenther, Wolfgang W. Schamel, Susana Minguet
Article
Multidisciplinary Sciences
Robert S. Washburn, Philipp K. Zuber, Ming Sun, Yaser Hashem, Bingxin Shen, Wen Li, Sho Harvey, Francisco J. Acosta Reyes, Max E. Gottesman, Stefan H. Knauer, Joachim Frank
Article
Biochemistry & Molecular Biology
Anna K. L. Liess, Alena Kucerova, Kristian Schweimer, Doerte Schlesinger, Olexandr Dybkov, Henning Urlaub, Joerg Mansfeld, Sonja Lorenz
Correction
Immunology
Frederike A. Hartl, Esmeralda Beck-Garcia, Nadine M. Woessner, Lea J. Flachsmann, Rubi M. -H. Velasco Cardenas, Simon M. Brandl, Sanaz Taromi, Gina J. Fiala, Anna Morath, Pankaj Mishra, O. Sascha Yousefi, Julia Zimmermann, Nico Hoefflin, Maja Koehn, Birgitta M. Woehrl, Robert Zeiser, Kristian Schweimer, Stefan Guenther, Wolfgang W. Schamel, Susana Minguet
Summary: An updated version of the paper has been published with a link provided at the top for easy access.
Article
Biochemistry & Molecular Biology
Pascal Kroeger, Sooruban Shanmugaratnam, Noelia Ferruz, Kristian Schweimer, Birte Hoecker
Summary: Periplasmic binding proteins (PBPs) are ubiquitous receptors in gram-negative bacteria that sense solutes and play key roles in nutrient uptake. Escherichia coli's putrescine receptor PotF has been reported to bind putrescine and spermidine. We reveal that several similar biogenic polyamines are recognized by PotF using isothermal titration calorimetry paired with X-ray crystallography of the different complexes. The analysis of ligand influence on complex formation is crucial, and structural behavior in solution for all complexes has been accessed by H-1-N-15 HSQC NMR spectroscopy. This combined analysis provides a robust framework for understanding ligand binding for future developments in drug design and protein engineering.
Article
Biophysics
Blanca Lopez-Mendez, Bruno Baron, Chad A. Brautigam, Thomas A. Jowitt, Stefan H. Knauer, Stephan Uebel, Mark A. Williams, Arthur Sedivy, Olga Abian, Celeste Abreu, Malgorzata Adamczyk, Wojciech Bal, Sylvie Berger, Alexander K. Buell, Carlo Carolis, Tina Daviter, Alexander Fish, Maria Garcia-Alai, Christian Guenther, Josef Hamacek, Jitka Holkova, Josef Houser, Chris Johnson, Sharon Kelly, Andrew Leech, Caroline Mas, Daumantas Matulis, Stephen H. McLaughlin, Roland Montserret, Rouba Nasreddine, Reine Nehme, Quyen Nguyen, David Ortega-Alarcon, Kathryn Perez, Katja Pirc, Grzegorz Piszczek, Marjetka Podobnik, Natalia Rodrigo, Jasmina Rokov-Plavec, Susanne Schaefer, Tim Sharpe, June Southall, David Staunton, Pedro Tavares, Ondrej Vanek, Michael Weyand, Di Wu
Summary: Microscale thermophoresis (MST) and Temperature Related Intensity Change (TRIC) are newly developed measurement techniques used to quantify biomolecular interactions, but have not been as widely accepted as other biophysical techniques. A benchmark study was conducted to assess the reliability of MST/TRIC in characterizing biomolecular interactions, involving multiple scientific groups across Europe and the US, utilizing standardized procedures and centrally prepared samples.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Editorial Material
Multidisciplinary Sciences
Ario de Marco, Nick Berrow, Mario Lebendiker, Maria Garcia-Alai, Stefan H. Knauer, Blanca Lopez-Mendez, Andre Matagne, Annabel Parret, Kim Remans, Stephan Uebel, Bertrand Raynal
Summary: Proteins and peptides are commonly used research reagents, but inadequate quality can lead to poor data reproducibility. Proposed guidelines aim to improve the reliability of experimental data when applied correctly to protein reagents.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Julia Dietler, Roman Schubert, Tobias G. A. Krafft, Simone Meiler, Stephanie Kainrath, Florian Richter, Kristian Schweimer, Michael Weyand, Harald Janovjak, Andreas Moeglich
Summary: Sensory photoreceptors can regulate the physiology, behavior, and development of organisms in response to light, making them useful in optogenetics for controlling diverse cellular processes. This study demonstrates that certain LOV modules can modulate protein expression by light, and some photoreceptors can also function as temperature sensors, potentially impacting their applications in optogenetics and biotechnology.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Correction
Biophysics
Blanca Lopez-Mendez, Bruno Baron, Chad A. Brautigam, Thomas A. Jowitt, Stefan H. Knauer, Stephan Uebel, Mark A. Williams, Arthur Sedivy, Olga Abian, Celeste Abreu, Malgorzata Adamczyk, Wojciech Bal, Sylvie Berger, Alexander K. Buell, Carlo Carolis, Tina Daviter, Alexander Fish, Maria Garcia-Alai, Christian Guenther, Josef Hamacek, Jitka Holkova, Josef Houser, Chris Johnson, Sharon Kelly, Andrew Leech, Caroline Mas, Daumantas Matulis, Stephen H. McLaughlin, Roland Montserret, Rouba Nasreddine, Reine Nehme, Quyen Nguyen, David Ortega-Alarcon, Kathryn Perez, Katja Pirc, Grzegorz Piszczek, Marjetka Podobnik, Natalia Rodrigo, Jasmina Rokov-Plavec, Susanne Schaefer, Tim Sharpe, June Southall, David Staunton, Pedro Tavares, Ondrej Vanek, Michael Weyand, Di Wu
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Sandra Weiss, Ramona S. Adolph, Kristian Schweimer, Andrea DiFonzo, Marat Meleshin, Mike Schutkowski, Clemens Steegborn
Summary: Sirt1, an important protein deacylase, is regulated by the interaction with the regulator protein AROS. AROS acts as a competitive inhibitor, inhibiting the activity of Sirt1. The findings provide molecular insights into the physiological regulation of Sirt1 and potential opportunities for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Philipp K. Zuber, Tina Daviter, Ramona Heissmann, Ulrike Persau, Kristian Schweimer, Stefan H. Knauer
Summary: This study investigates the thermodynamic stability and structural dynamics of two-domain protein RfaH and NusG/Spt5-KOW domains. The findings suggest that the folding transition in RfaH is driven by transiently structured elements in the unfolded conformation.
Article
Biology
Ramona S. Adolph, Eileen Beck, Kristian Schweimer, Andrea Di Fonzo, Michael Weyand, Paul Roesch, Birgitta M. Woehrl, Clemens Steegborn
Summary: Sirtuins are NAD(+)-dependent protein lysine deacylases involved in metabolic regulation and aging-related dysfunctions. Sirt1, a nuclear isoform, deacetylates histones and transcription factors, contributing to brain and immune cell functions. In HIV1 infection, Sirt1 promotes viral genome expression by deacetylating the viral transactivator of transcription (Tat) protein. However, Tat inhibits Sirt1, leading to T cell hyperactivation associated with HIV infection.