Article
Biotechnology & Applied Microbiology
Javier Garcia-Pardo, Aleksandra E. Badaczewska-Dawid, Carlos Pintado-Grima, Valentin Iglesias, Aleksander Kuriata, Sebastian Kmiecik, Salvador Ventura
Summary: This study presents the A3D yeast database (A3DyDB), which provides an extensive catalog of aggregation propensity predictions for the S. cerevisiae proteome, allowing for the evaluation of the influence of mutations on protein stability and solubility.
MICROBIAL CELL FACTORIES
(2023)
Article
Biochemistry & Molecular Biology
Daohan Jiang, Alexander L. Cope, Jianzhi Zhang, Matt Pennell
Summary: Variation in gene expression across lineages plays a crucial role in explaining phenotypic variation and adaptation. However, the assumption that mRNA levels can accurately represent protein levels has been challenged by studies showing weak correlations between the two measures across species. This discrepancy might be due to compensatory evolution between mRNA levels and translation regulation, but the conditions and strength of the correlation are still not well understood. A theoretical model of the coevolution of mRNA and protein levels reveals that compensatory evolution is common with stabilizing selection on protein levels, while under directional selection, mRNA levels and translation rates show negative correlations across lineages but positive correlations across genes. These findings offer insights into comparative studies of gene expression and provide a framework to distinguish biological and statistical hypotheses for the transcriptomic-proteomic mismatch.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Giovanni Smaldone, Daniela Caruso, Annamaria Sandomenico, Emanuela Iaccarino, Annalia Foca, Alessia Ruggiero, Menotti Ruvo, Luigi Vitagliano
Summary: The three members of the GADD45 protein family are involved in diverse cellular functions, with GADD45 beta and GADD45 gamma showing marginal stability at physiological temperatures and GADD45 alpha demonstrating a higher stability and presence of amyloid-like aggregate properties. These unique characteristics may have important implications for their cytotoxicity and functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Psychiatry
Haiqing Zhang, Yuhang Gu, Wenxiang He, Fengyi Kuo, Yiran Zhang, Duan Wang, Li He, Ying Yang, Hepeng Wang, Yanni Chen
Summary: Abnormal alterations in enzymes involved in sialic acid modifications may be associated with autism spectrum disorder (ASD). This study found that NEU1 mRNA expression in peripheral blood of children with ASD was significantly higher than in healthy controls, and it was correlated with social affect in children with ASD.
FRONTIERS IN PSYCHIATRY
(2022)
Review
Immunology
Leonardo Cortazzo da Silva, Juliana Ide Aoki, Lucile Maria Floeter-Winter
Summary: This study analyzed the transcriptomic and proteomic data of two different stages in the Leishmania life cycle and found a correlation between mRNA and protein levels. The majority of genes showed concurrent changes in mRNA and protein levels, while some genes did not exhibit correlation. This research is important for understanding the gene expression regulation mechanisms in Leishmania.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Agata Bancerz-Kisiel, Karolina Lipczynska-Ilczuk
Summary: This study aimed to analyze the expression of ystA and ymoA genes in Y. enterocolitica strains isolated from humans and pigs with different enterotoxic properties. The results showed a correlation between mRNA expression levels of ystA and ymoA genes in Y. enterocolitica strains isolated from humans, with significant differences observed in strains causing clinical symptoms of yersiniosis. Strains isolated from pigs did not show statistically significant differences in gene expression levels.
Article
Biochemistry & Molecular Biology
Tasuku Nishino, Tsuyoshi Oshika, Moriatsu Kyan, Hiroaki Konishi
Summary: The study investigated the subcellular localization of GAREM1 and GAREM2 in response to cell growth stimulus. It was found that GAREM2 specifically formed granules in response to NGF and EGF stimulation, and a glycine-rich region in GAREM2 was required for this granule formation. This aggregation of GAREM2 may be linked to neurodegenerative diseases.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2021)
Article
Genetics & Heredity
Buyue Niu, Lu Liu, Zhihua Chen, Mingxing Kou, Xiuqin Yang, Yuan Sun, Shengwei Di, Xibiao Wang, Jiancheng Cai, Dongchun Guo
Summary: Matrix metalloproteinase 7 (MMP7) plays a crucial role in the degradation of extracellular matrix during disease processes, impacting host disease resistance/susceptibility. In this study, the porcine MMP7 (pMMP7) gene was characterized, genetic variations in pMMP7 were identified, and the relationship between pMMP7 polymorphisms and piglets diarrhea in Min pig and Landrace populations was explored. The findings provide insights into the biological function of pMMP7 and offer potential molecular markers for pig breeding.
Article
Nanoscience & Nanotechnology
Larissa Fernanda Ferreira, Agustin Silvio Picco, Flavia Elisa Galdino, Lindomar Jose Calumby Albuquerque, Jean-Francois Berret, Mateus Borba Cardoso
Summary: The formation of protein corona and nanoparticles' aggregation has hindered the development of targeted delivery and personalized nanomedicine. This study presents a multitechnique approach that efficiently distinguishes protein corona from aggregates formation, which can be used as a quality control platform for samples.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Anna M. Schlagowski, Katharina Knoringer, Sandrine Morlot, Ana Sanchez Vicente, Tamara Flohr, Lena Kraemer, Felix Boos, Nabeel Khalid, Sheraz Ahmed, Jana Schramm, Lena M. Murschall, Per Haberkant, Frank Stein, Jan Riemer, Benedikt Westermann, Ralf J. Braun, Konstanze F. Winklhofer, Gilles Charvin, Johannes M. Herrmann
Summary: The study investigates the regulation of aggregation-prone polyQ protein behavior by mitochondrial processes, revealing that Mia40 plays a rate-limiting role in the import of mitochondrial precursor proteins and can be exploited to stabilize cytosolic proteostasis.
Article
Multidisciplinary Sciences
Zarmik Moqtaderi, Joseph V. Geisberg, Kevin Struhl
Summary: There is a compensatory link between cleavage/polyadenylation in the nucleus and mRNA turnover in the cytoplasm. Same-gene 30 mRNA isoforms with different half-lives have similar steady-state mRNA levels, indicating an inverse relationship between cleavage/polyadenylation and mRNA isoform stability.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Yuexu Jiang, Lei Jiang, Chopparapu Sai Akhil, Duolin Wang, Ziyang Zhang, Weinan Zhang, Dong Xu
Summary: The study introduces a new web application based on MULocDeep, which has improved performance, result interpretation, and visualization, for predicting protein localization and understanding its mechanisms. By transferring the original model into species-specific models, MULocDeep achieves competitive prediction performance at the subcellular level compared to other state-of-the-art methods. Besides localization prediction, the web service quantifies the contribution of single amino acids to localization for individual proteins and derives common motifs or potential targeting-related regions for a group of proteins. The visualizations of targeting mechanism analyses can be downloaded for publication-ready figures. The MULocDeep web service is available at https://www.mu-loc.org/.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Horticulture
Jianhua Luo, Yue Zhou, Qinwei Pan, Qin Mu, Tingting Gu
Summary: YABBY (YAB) transcription factors play crucial roles in leaf and fruit development. Six YAB proteins were identified in woodland strawberry and 25 in cultivated strawberry, with some showing up-regulation during fruit ripening. ChIP experiments revealed enrichment of certain YAB proteins in active histone marks in red fruits. Furthermore, transcript levels of specific YAB genes were found to be responsive to temperature stress.
SCIENTIA HORTICULTURAE
(2022)
Article
Multidisciplinary Sciences
Hubert Wyszkowski, Anna Janta, Wiktoria Sztangierska, Igor Obuchowski, Tomasz Chamera, Agnieszka Klosowska, Krzysztof Liberek
Summary: The study investigates the functional differences between two classes of JDPs in yeast during the process of protein disaggregation, highlighting the superior aggregate binding ability of Ydj1 and the recruitment of more Ssa1 molecules to substrates by Sis1, which depends on its specific binding mechanism with Hsp70. These findings suggest that the subspecialization of JDPs during protein reactivation improves the robustness and efficiency of the disaggregation machinery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Pengju Zhao, Xianrui Zheng, Ying Yu, Zhuocheng Hou, Chenguang Diao, Haifei Wang, Huimin Kang, Chao Ning, Junhui Li, Wen Feng, Wen Wang, George E. Liu, Bugao Li, Jacqueline Smith, Yangzom Chamba, Jian-Feng Liu
Summary: This study identified a large number of unknown protein isoforms from normal pig tissues and systematically characterized them, enhancing the study of the pig proteome. Through high-throughput RNA sequencing, the functional annotations of these newly identified protein isoforms were analyzed, providing a basis for further improving genome annotation. Finally, a significant number of orthologous genes for unknown protein isoforms across multiple species were mined, referencing various pathways and providing valuable resources for pig genomics and biology research.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Riccardo Delli Ponti, Laura Broglia, Andrea Vandelli, Alexandros Armaos, Marc Torrent Burgas, Natalia Sanchez de Groot, Gian Gaetano Tartaglia
Summary: RNA molecules undergo chemical modifications that can alter their structure and molecular interactions. This study introduces a predictor of A-to-I effects on RNA structure and finds enrichment of double-stranded regions caused by A-to-I in long intergenic noncoding RNAs. Investigation of specific cases suggests that A-to-I editing is linked to the alteration of interaction sites with proteins involved in phase separation.
Article
Biochemical Research Methods
Marc Oeller, Ryan Kang, Rosie Bell, Hannes Ausserwoger, Pietro Sormanni, Michele Vendruscolo
Summary: This article describes a computational method that incorporates the effect of pH on protein solubility predictions. The accuracy of these predictions is comparable to experimental methods, as demonstrated on various antibodies and proteins. This method, named CamSol 3.0, is now publicly available at https://www-cohsoftware.ch.cam.ac.uk/index.php/camsolph.
BRIEFINGS IN BIOINFORMATICS
(2023)
Review
Chemistry, Multidisciplinary
Ryan Limbocker, Nunilo Cremades, Roberta Cascella, Peter M. Tessier, Michele Vendruscolo, Fabrizio Chiti
Summary: The misfolding and aggregation of peptides and proteins into amyloid aggregates is a common feature of various protein misfolding diseases, including Alzheimer's disease and Parkinson's disease. Misfolded protein oligomers, which can form intermediates in the fibril formation process or be released by mature fibrils, are increasingly recognized as central to the development of these diseases. Despite challenges in studying these oligomers, researchers have developed methods to produce stable and reproducible populations for experimentation. These tools have provided insights into the structural determinants of oligomer toxicity and potential therapeutic strategies.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Review
Pharmacology & Pharmacy
Michele Vendruscolo
Summary: Protein misfolding diseases, such as Alzheimer's and Parkinson's diseases, have a major impact on our healthcare systems and societies. This paper discusses drug discovery strategies to target protein misfolding and aggregation, including thermodynamic and kinetic approaches. There is a need for disease-modifying treatments to address the over 50 human disorders associated with protein misfolding and aggregation.
EXPERT OPINION ON DRUG DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Alessio Colantoni, Davide Capauto, Vincenzo Alfano, Eleonora D'Ambra, Sara D'Uva, Gian Gaetano Tartaglia, Mariangela Morlando
Summary: Deregulation of RNA metabolism, specifically mutations on RNA-binding proteins (RBPs) or on proteins involved in RNA metabolism, is a key factor in the degeneration of motor neurons in ALS. The ALS-linked mutation of the RBP FUS greatly affects various RNA-related processes, including splicing regulation and circRNA formation. In this study, the impact of the FUS mutation on circRNA levels and its binding preferences were investigated using in vitro-derived human motor neurons. The findings suggest potential implications of cytoplasmic circRNAs as miRNA sponges in ALS pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Mark R. Wilson, Sandeep Satapathy, Michele Vendruscolo
Summary: The proteostasis system regulates cellular processes of protein synthesis, folding, concentration, trafficking, and degradation. The mechanisms of extracellular proteostasis, particularly in the context of neurodegenerative diseases, are not well understood, but growing evidence suggests that impairment of this system may contribute to neuronal death.
NATURE REVIEWS NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Andras Hatos, Joao M. C. Teixeira, Susana Barrera-Vilarmau, Attila Horvath, Silvio C. E. Tosatto, Michele Vendruscolo, Monika Fuxreiter
Summary: Proteins form complex interactions in the cellular environment. The FuzPred server predicts their binding modes based on sequence without specifying the binding partners. The server also estimates the multiplicity of binding modes and visualizes different interaction behaviors on protein structures.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Alyssa Miller, Jiapeng Wei, Sarah Meehan, Christopher M. Dobson, Mark E. Welland, David Klenerman, Michele Vendruscolo, Francesco Simone Ruggeri, Tuomas P. J. Knowles
Summary: Neurodegenerative diseases such as Alzheimer's disease are caused by protein misfolding and aggregation into amyloid fibrils. This study uses atomic force microscopy and statistical theory to characterize amyloid ring structures derived from the brains of AD patients and explains the diversity in the structures formed from protein aggregation. The results show that ex vivo protofibril chains possess greater flexibility than mature amyloid fibrils, allowing them to form end-to-end connections and shedding light on their role in disease.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Nuria Crua Asensio, Stefano Rizzieri, Alessandro Cuomo, Gian Gaetano Tartaglia, Elsa Zacco
Summary: Protein-RNA interactions are crucial for gene expression and cellular functions. To efficiently identify the binding partners of RNA molecules, especially non-canonical ones, an improved method was developed. This method involves pull-down and characterization of interacting proteins using biotinylated RNA loaded on streptavidin-coated beads. The protocol was validated by quantifying the enrichment of a known RNA binder compared to a negative control using mass spectrometry and confirming the selective interactions of computationally predicted protein binders by western blot. This protocol allows for the study of protein-RNA interactions in near-physiological conditions, aiding in the discovery of unique and unpredicted interactions.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2023)
Editorial Material
Biochemistry & Molecular Biology
Andre P. Gerber, Gian Gaetano Tartaglia
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Z. Faidon Brotzakis, Thomas Lohr, Steven Truong, Samuel Hoff, Massimiliano Bonomi, Michele Vendruscolo
Summary: In recent years, cryo-electron microscopy has made significant advancements in determining biomolecular structures at the atomic level. However, studying large systems with continuous dynamics using this method has been a challenge. To address this, the metadynamic electron microscopy metainference (MEMMI) method was developed, which combines cryo-EM density maps with prior information to determine the structure and dynamics of large heterogeneous systems. This method was applied to study the amyloid fibril dynamics of the islet amyloid polypeptide (IAPP), revealing interesting characteristics of the fibril's structural variability and liquid-like dynamics in the core region.
Article
Biochemistry & Molecular Biology
Jakob Rupert, Michele Monti, Elsa Zacco, Gian Gaetano Tartaglia
Summary: This study characterizes the physico-chemical properties of regions involved in amyloid aggregation using a computational approach, and investigates the influence of RNA on protein assembly. Experimental data shows that while the core region is hydrophobic and highly ordered, external regions exhibit a distinct tendency to interact with nucleic acids. RNA is found to accelerate aggregation, especially in a mutant truncated protein with a higher propensity for RNA interaction. The findings suggest that RNA sequestration might be a common phenomenon linked to protein aggregation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Christine M. Lim, Alicia Gonzalez Diaz, Monika Fuxreiter, Frank W. Pun, Alex Zhavoronkov, Michele Vendruscolo
Summary: This study presents an approach that combines the PandaOmics platform with the FuzDrop method to identify disease-associated proteins prone to protein phase separation (PPS). The validated targets for Alzheimer's disease suggest the potential of this approach in identifying therapeutic targets for diseases involving dysregulation of PPS.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemical Research Methods
Andrea Vandelli, Magdalena Arnal Segura, Michele Monti, Jonathan Fiorentino, Laura Broglia, Alessio Colantoni, Natalia Sanchez de Groot, Marc Torrent Burgas, Alexandros Armaos, Gian Gaetano Tartaglia
Summary: PRALINE is a database that provides information on protein-protein, protein-RNA, and RNA-RNA interactions in stress granules, processing bodies, and other assemblies. It also reports the liquid-liquid and liquid-solid phase separation propensities of proteins and provides predicted secondary structure content of RNAs.
Article
Biochemistry & Molecular Biology
Thomas Schwarzl, Sudeep Sahadevan, Benjamin Lang, Milad Miladi, Rolf Backofen, Wolfgang Huber, Matthias W. Hentze, Gian Gaetano Tartaglia
Summary: Enhanced crosslinking and immunoprecipitation sequencing (eCLIP-seq) is a method for detecting RNA-binding protein binding sites. However, current analysis strategies have low replication and high false positive rates. DEWSeq, a R/Bioconductor package, improves the detection of binding regions by utilizing replicate information and size-matched input controls. It has been shown to significantly increase the number and quality of binding sites.
NUCLEIC ACIDS RESEARCH
(2023)
