Article
Biochemistry & Molecular Biology
Adriano Biasini, Baroj Abdulkarim, Stefano de Pretis, Jennifer Y. Tan, Rajika Arora, Harry Wischnewski, Rene Dreos, Mattia Pelizzola, Constance Ciaudo, Ana Claudia Marques
Summary: Translation is necessary for miRNA-dependent transcript destabilization, and coding and noncoding transcripts are differently affected by miRNAs.
Article
Biology
Sibylle Mitschka, Christine Mayr
Summary: The study discovered that the endogenous 3'UTR does not play a role in regulating p53 expression in tumors. CRISPR/Cas9 experiments revealed this phenomenon while also confirming the repressive effects of the 3'UTR.
Article
Multidisciplinary Sciences
Jared S. Elenbaas, Upasana Pudupakkam, Katrina J. Ashworth, Chul Joo Kang, Ved Patel, Katherine Santana, In-Hyuk Jung, Paul C. Lee, Kendall H. Burks, Junedh M. Amrute, Robert P. Mecham, Carmen M. Halabi, Arturo Aliso, Jorge Di Paola, Nathan O. Stitziel
Summary: The study identifies a high affinity interaction between SVEP1 and the orphan receptor PEAR1, which promotes phosphorylation of PEAR1 and activation of AKT/mTOR signaling in vascular cells and platelets. Mice lacking SVEP1 exhibit reduced platelet activation, while exogenous SVEP1 induces PEAR1-dependent activation of platelets. Targeting this receptor-ligand interaction may offer a potential therapeutic strategy for cardiovascular and thrombotic diseases.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Jose Tomas Canovas-Marquez, Sebastian Falk, Francisco E. Nicolas, Subramanian Padmanabhan, Ruben Zapata-Perez, Alvaro Sanchez-Ferrer, Eusebio Navarro, Victoriano Garre
Summary: RNase III family members regulate gene expression by processing dsRNA, and the fungus Mucor lusitanicus has a complex RNAi system including a non-canonical NCRIP pathway. R3B2 forms a homodimer that binds to and cuts ssRNA, but not dsRNA, due to its unusual RNase III domain structure.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Cell Biology
MengWen Huang, Ling Lu, ChangDong Lin, YaJuan Zheng, XingChao Pan, ShiHui Wang, ShiYang Chen, YouHua Zhang, ChunYe Liu, GaoXiang Ge, Yi Arial Zeng, JianFeng Chen
Summary: Dynamic regulation of integrin activation and inactivation is crucial for cell adhesion and migration. LRP12 is identified as a transmembrane inhibitor for a4 integrin activation, maintaining the balance of nascent adhesion turnover and controlling cell migration. Knockdown of LRP12 leads to increased nascent adhesions and enhanced cell migration.
Article
Cell Biology
Valeria Runfola, Roberto Giambruno, Claudia Caronni, Maria Pannese, Annapaola Andolfo, Davide Gabellini
Summary: This article investigates the molecular mechanism of Facioscapulohumeral muscular dystrophy (FSHD) and identifies Matrin 3 (MATR3) as a potential candidate for developing treatment for this disease.
Article
Developmental Biology
Daniel O'Hagan, Robin E. Kruger, Bin Gu, Amy Ralston
Summary: Two strategies for higher throughput production of endogenous protein reporters in mice were presented, utilizing split fluorescent protein mNeonGreen2 and in-frame knock-in of a relatively small protein tag, providing high efficiency and sensitivity for protein reporting, enabling broad downstream applications.
Article
Cell Biology
Wenjing Chen, Yuxing Li, Gui-Xin Ruan, Hengjun Huang, Rui Zhang, Jing Wang, Yu Ouyang, Yan Li, Shengli Xu, Xijun Ou
Summary: ADAR1 plays a crucial role in early B lymphopoiesis through both MDA5-dependent and -independent mechanisms.
Article
Medical Laboratory Technology
Khanh Quynh N. Nguyen, Rachel H. Langevin, Michael J. McPhaul, Ibrahim A. Hashim
Summary: Macroprolactin (macPRL) was found to exhibit heterogeneity in samples, possibly due to factors such as antibody binding or glycosylated aggregates. Samples with (H) and (M) macPRL forms showed significant positive bias in two of the four immunoassay analysers used. Further studies on a larger scale are required due to the limited sample size.
CLINICA CHIMICA ACTA
(2021)
Article
Multidisciplinary Sciences
Flavia A. Graca, Mamta Rai, Liam C. Hunt, Anna Stephan, Yong-Dong Wang, Brittney Gordon, Ruishan Wang, Giovanni Quarato, Beisi Xu, Yiping Fan, Myriam Labelle, Fabio Demontis
Summary: Myofiber atrophy is a key feature of cancer-induced wasting, and the muscle-secreted factor Fibcd1 plays an important role in maintaining myofiber size and mitigating atrophy induced by cachexia.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
James Chen, Alice Fruhauf, Catherine Fan, Jackeline Ponce, Beatrix Ueberheide, Gira Bhabha, Damian C. Ekiert
Summary: To cause tuberculosis, Mycobacterium tuberculosis needs to obtain nutrients from the host cells. The MCE proteins, encoded by gene clusters, play a crucial role in the virulence of M. tuberculosis by transporting fatty acids and cholesterol across the impermeable mycobacterial cell envelope. This study reveals the cryo-EM structure of the Mce1 lipid-import machine in Mycobacterium smegmatis and provides insights into the mechanism of lipid transport across the mycobacterial cell envelope.
Article
Biochemistry & Molecular Biology
Labib Rouhana, Allison Edgar, Fredrik Hugosson, Valeria Dountcheva, Mark Q. Martindale, Joseph F. Ryan
Summary: Differential regulation of gene expression is crucial for the astonishing diversity of life on Earth. Cytoplasmic polyadenylation, mediated by the CPEB family, regulates the translation of maternal transcripts and is present in animals but not non-animal lineages. Phylogenetic analyses reveal that CPEB1 and CPEB2 originated in the animal stem lineage. This study demonstrates the conservation of maternal expression and polyadenylation targets in cnidarians, ctenophores, and vertebrates, suggesting that cytoplasmic polyadenylation through CPEBs was a fundamental innovation in animal evolution.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Akiko Ogawa, Chisae Nagiri, Wataru Shihoya, Asuka Inoue, Kouki Kawakami, Suzune Hiratsuka, Junken Aoki, Yasuhiro Ito, Takeo Suzuki, Tsutomu Suzuki, Toshihiro Inoue, Osamu Nureki, Hidenobu Tanihara, Kazuhito Tomizawa, Fan-Yan Wei
Summary: The study identified N-6-methyladenosine (m(6)A) as a ligand for the human adenosine A3 receptor with higher affinity than unmodified adenosine. Structural modeling revealed the amino acids required for specific binding of m(6)A to the human A3 receptor and demonstrated its dynamic release in response to cytotoxic stimuli and facilitation of type I allergy in vivo. These findings suggest m(6)A as a signaling molecule capable of activating G protein-coupled receptors (GPCRs) and triggering pathophysiological responses, a previously unreported property of RNA modifications.
Article
Clinical Neurology
Giulia E. Tyzack, Jacob Neeves, Hamish Crerar, Pierre Klein, Oliver Ziff, Doaa M. Taha, Raphaelle Luisier, Nicholas M. Luscombe, Rickie Patani
Summary: The study identified over 100 IRTs with increased cytoplasmic abundance in ALS, showing sequence-specific attributes and differential binding affinity to RNA binding proteins such as TDP-43, SFPQ, and FUS. This provides new molecular insights into potential pathomechanisms underlying ALS and highlights aberrant cytoplasmic IRTs as potential therapeutic targets.
Article
Biochemistry & Molecular Biology
Yuan Li, Yufeng Jia, Dongdong Wang, Xiao Zhuang, Yan Li, Chun Guo, Hongxia Chu, Faliang Zhu, Jianing Wang, Xiaoyan Wang, Qun Wang, Wei Zhao, Yongyu Shi, Wanjun Chen, Lining Zhang
Summary: This study revealed that Pdcd4 acts as an endogenous inhibitor for BDNF translation and provided a novel approach for enhancing BDNF expression by blocking Pdcd4 function. These findings suggest that targeting Pdcd4 may be a promising strategy for treating depressive disorders.
MOLECULAR PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Itaru Samejima, Christos Spanos, Kumiko Samejima, Juri Rappsilber, Georg Kustatscher, William C. Earnshaw
Summary: We have used multiple techniques including chemical genetics, chromatin proteomics, and imaging to study the earliest chromatin transactions during cell entry into mitosis. Our findings reveal significant changes in the association of ribonucleoproteins with chromatin during the early stages of mitosis, as well as the loss of nuclear envelope barrier function and accumulation of cytoplasmic proteins on chromatin. These results provide valuable insights into the dynamics of chromatin during mitotic entry.
Article
Chemistry, Analytical
Lars Kolbowski, Swantje Lenz, Lutz Fischer, Ludwig R. Sinn, Francis J. O'Reilly, Juri Rappsilber
Summary: This study examines the advantages and disadvantages of using MS-cleavable crosslinkers in proteome-wide crosslinking mass spectrometry studies. It is found that the main advantage of MS cleavability of the crosslinker is improved peptide backbone fragmentation, reducing the ambiguity of peptide identifications. Additionally, simpler and faster HCD method outperforms more intricate MS3-based data acquisition approaches.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Christian Much, Michael J. Smallegan, Taeyoung Hwang, Skylar D. Hanson, Gabrijela Dumbovic, John L. Rinn
Summary: The research shows that the syntenically conserved lncRNA Firre displays distinct expression and localization patterns in humans and mice. Mouse Firre is predominantly located in the nucleus, while human FIRRE is distributed between the cytoplasm and nucleus. The localization of the lncRNA is believed to be species autonomous when expressed in human/mouse hybrid cells. The majority of hFIRRE transcripts in the cytoplasm contain isoforms enriched in RRD repeats, and mFirre is more highly expressed than its human counterpart in various tissues.
Article
Biochemistry & Molecular Biology
David Zapletal, Eliska Taborska, Josef Pasulka, Radek Malik, Karel Kubicek, Martina Zanova, Christian Much, Marek Sebesta, Valeria Buccheri, Filip Horvat, Irena Jenickova, Michaela Prochazkova, Jan Prochazka, Matyas Pinkas, Jiri Novacek, Diego F. Joseph, Radislav Sedlacek, Carrie Bernecky, Donal O'Carroll, Richard Stefl, Petr Svoboda
Summary: The DExD/H domain of Dicer plays a crucial structural role in mammalian miRNA biogenesis. It locks Dicer in a closed state, facilitating miRNA precursor selection. Absence or mutations of the DExD/H domain unlock Dicer and activate RNAi.
Article
Biology
Alexandro Landshammer, Adriano Bolondi, Helene Kretzmer, Christian Much, Rene Buschow, Alina Rose, Hua-Jun Wu, Sebastian D. Mackowiak, Bjoern Braendl, Pay Giesselmann, Rosaria Tornisiello, Krishna Mohan Parsi, Jack Huey, Thorsten Mielke, David Meierhofer, Rene Maehr, Denes Hnisz, Franziska Michor, John L. Rinn, Alexander Meissner
Summary: In this study, a previously unannotated lncRNA, T-REX17, was discovered upstream of the SOX17 gene. It was found to be induced following SOX17 activation and its expression was specifically restricted to early definitive endoderm. Loss of T-REX17 affected important functions independent of SOX17 and resulted in an aberrant endodermal transcriptome, signaling pathway deregulation, and defects in epithelial to mesenchymal transition. Consequently, cells lacking T-REX17 were unable to differentiate into more mature endodermal cell types. Overall, this study identified and characterized T-REX17 as a transiently expressed and essential non-coding regulator in early human endoderm differentiation.
Article
Biochemistry & Molecular Biology
Zhuo Angel Chen, Juri Rappsilber
Summary: Crosslinking mass spectrometry captures protein structures in solution, revealing spatial proximities and conformation-specific crosslinks. Advances in crosslinking MS, such as photoactivatable crosslinking and in-situ crosslinking, will enable the study of protein conformation dynamics at a pseudo-atomic resolution in the cellular context and potentially in a time-resolved manner.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Article
Chemistry, Medicinal
Ana M. Perez-Lopez, Adam Belsom, Linus Fiedler, Xiaoyi Xin, Juri Rappsilber
Summary: Artificial metalloenzymes (ArMs) enhance bioorthogonal chemistry by introducing new reactions and minimizing metal deactivation and toxicity, enabling the activation of therapeutics in vivo.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Georg Kustatscher, Martina Hodl, Edward Rullmann, Piotr Grabowski, Emmanuel Fiagbedzi, Anja Groth, Juri Rappsilber
Summary: Operons are transcriptional modules that allow bacteria to adapt to environmental changes by coordinating the expression of relevant genes. In humans, the coordination of entire biological processes is unclear. Using machine-learning on proteomics data, we identified 31 higher-order co-regulation modules, called progulons, which consist of proteins that mediate core cellular functions. Progulon abundance changes are primarily controlled at the level of protein synthesis and degradation. By implementing our approach as a web app, we can search for progulons of specific cellular processes and identify new replication factors.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Francis J. O'Reilly, Andrea Graziadei, Christian Forbrig, Rica Bremenkamp, Kristine Charles, Swantje Lenz, Christoph Elfmann, Lutz Fischer, Joerg Stuelke, Juri Rappsilber
Summary: Accurately modeling protein structures and their complexes using AI is revolutionizing molecular biology. In this study, we used a combination of crosslinking mass spectrometry and CoFrac-MS to identify protein-protein interactions in a Gram-positive bacterium. By predicting the structures of these interactions and validating them with crosslinking MS data, we proposed novel structural models of protein assemblies and identified new interactors of important cellular machineries. This approach provides insights into protein-protein interactions inside intact cells and is applicable to genetically intractable organisms.
MOLECULAR SYSTEMS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Belen Pacheco-Fiallos, Matthias K. Vorlaender, Daria Riabov-Bassat, Laura Fin, Francis J. O'Reilly, Farja I. Ayala, Ulla Schellhaas, Juri Rappsilber, Clemens Plaschka
Summary: Newly made mRNAs are recognized and organized by the essential TREX complex for nuclear export. Cryo-electron microscopy and tomography structures reveal that mRNAs are recognized through multivalent interactions between TREX subunit ALYREF and mRNP-bound exon junction complexes. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes, providing a framework to understand mRNA biogenesis and export.
Article
Biotechnology & Applied Microbiology
Kolja Stahl, Andrea Graziadei, Therese Dau, Oliver Brock, Juri Rappsilber
Summary: Limitations of Alphafold2 structure prediction are overcome by incorporating experimentally determined distance constraints using AlphaLink. This modified version improves prediction for challenging targets by utilizing sparse experimental contacts and can predict distinct protein conformations. Experimental data on residue-residue contacts obtained through crosslinking mass spectrometry validates the improved performance. The noise-tolerant framework for integrating data allows accurate characterization of protein structures from in-cell data.
NATURE BIOTECHNOLOGY
(2023)
Article
Chemistry, Analytical
Lars Kolbowski, Lutz Fischer, Juri Rappsilber
Summary: Cross-linking mass spectrometry is transitioning to enable structural systems biology, with MS3-based approaches for identifying cross-linked peptides showing potential despite MS2-based methods currently outperforming.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Nitobe London, Bethan Medina-Pritchard, Christos Spanos, Juri Rappsilber, A. Arockia Jeyaprakash, Robin C. Allshire
Summary: During G2, fission yeast centromeres cluster at SPBs, where Mis18C also localizes. It is shown that SPBs concentrate Mis18C near centromeres through direct binding to Sad1. This centromere-independent Mis18-SPB recruitment mechanism regulates the assembly of CENP-ACnp1 chromatin at centromeres.
Article
Biochemistry & Molecular Biology
Eva Absmeier, Viswanathan Chandrasekaran, Francis J. O'Reilly, James A. W. Stowell, Juri Rappsilber, Lori A. Passmore
Summary: This study demonstrates that mammalian CCR4-NOT can specifically recognize stalled ribosomes and stabilize the interaction through protein-protein interactions. The findings suggest that human CCR4-NOT not only detects ribosomal stalling but also links translation to mRNA decay through a specific signaling pathway.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Lars Kolbowski, Adam Belsom, Ana M. M. Perez-Lopez, Tony Ly, Juri Rappsilber
Summary: Crosslinking mass spectrometry is important for studying the structure and interaction of proteins. We have introduced orthogonal cleavage using ultraviolet photodissociation (UVPD) to increase the fragmentation of crosslinkers relative to peptides, which improves the selectivity for identifying individual peptides. By using this method, the crosslinker-to-peptide fragment intensity ratio increased from nearly 1 for a conventionally cleavable crosslinker to 5 for the UVPD-cleavable crosslinker in an analysis of crosslinked Escherichia coli lysate. This greatly enhanced the sensitivity for selecting individual peptides.