Article
Biochemistry & Molecular Biology
Kamil Filipek, Kamil Derylo, Barbara Michalec-Wawiorka, Monika Zaciura, Alan Gonzalez-Ibarra, Dawid Krokowski, Przemyslaw Latoch, Agata L. Starosta, Jakub Czapinski, Adolfo Rivero-Muller, Leszek Wawiorka, Marek Tchorzewski
Summary: Alternative splicing is a key mechanism that extends the complexity and adaptability of genetic information in higher eukaryotes. This study characterizes an alternatively spliced isoform of the ribosomal uL10 protein, uL108, and investigates its expression and localization within cells. The findings suggest a potential dual role of uL108 in response to stress, supporting the existence of specialized ribosomes with altered functionality.
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
(2023)
Article
Multidisciplinary Sciences
Shreyas Jadhav, Sudipta Tripathi, Anil Chandrekar, Sushrut S. Waikar, Li-Li Hsiao
Summary: The study identified two circulating isoforms of alpha Klotho and developed an antibody using a unique 15aa peptide sequence to specifically detect the secreted isoform in human plasma. This finding will enhance the potential of alpha Klotho isoforms as biomarkers for CKD and other conditions by facilitating the distinguishing of their levels in circulation.
Article
Biochemistry & Molecular Biology
Ashley Lui, Robert Sparks, Rekha Patel, Niketa A. Patel
Summary: This study identified a novel sortilin splice variant related to glucose metabolism, whose presence may be associated with insulin resistance in adipocytes. This finding provides a new potential target for the management of type 2 diabetes and metabolic syndrome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Qianying Guo, Hao Wang, Jiahao Duan, Wenwu Luo, Rongrong Zhao, Yuting Shen, Bijun Wang, Siqi Tao, Yi Sun, Qian Ye, Xiaomin Bi, Hui Yuan, Qiang Wu, Peter E. Lobie, Tao Zhu, Sheng Tan, Xing Huang, Zhengsheng Wu
Summary: A novel p62 mRNA isoform that escapes miRNA-mediated repression and leads to increased p62 protein expression was found to be associated with chemoresistance in breast cancer cells and tissue specimens.
Article
Biochemistry & Molecular Biology
Meng-Han Huang, Gui-Xin Peng, Xue-Ling Mao, Jin-Tao Wang, Jing-Bo Zhou, Jian-Hui Zhang, Meirong Chen, En-Duo Wang, Xiao-Long Zhou
Summary: The study identified different isoforms of METTL8 that play various roles in different cell compartments. The isoforms have distinct localization and show different mechanisms in the modification of mitochondrial tRNA. The interaction between SARS2 and METTL8-Iso1 was found to enhance the modification activity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Neurosciences
Benjamin C. Shaw, Henry C. Snider, Andrew K. Turner, Diana J. Zajac, James F. Simpson, Steven Estus
Summary: Genetic variants in the TREM2 gene are associated with Alzheimer's disease risk. This study comprehensively describes the alternative splicing of TREM2 transcripts. The researchers identified novel isoforms lacking exon 2, and found that these isoforms are translated into protein and expressed in both AD and non-AD brain. The study suggests that targeting TREM2 splicing may be a potential therapeutic pathway for AD.
JOURNAL OF ALZHEIMERS DISEASE
(2022)
Article
Medicine, Research & Experimental
Xiaobo Li, Yuanyuan Zhu, Xiao Zhang, Xiang An, Mingjiao Weng, Jiaqi Shi, Song Wang, Caiqi Liu, Shengnan Luo, Tongsen Zheng
Summary: The study reveals the signaling mechanism of STING base cGAMP in activating anti-tumor immune response. It identifies an alternatively spliced STING isoform, pmSTING, which can sense extracellular cGAMP on the plasma membrane and promote interferon production through interaction with TBK1 and IRF3.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Genetics & Heredity
Achala Fernando, Chamikara Liyanage, Afshin Moradi, Panchadsaram Janaththani, Jyotsna Batra
Summary: This study comprehensively characterized IRX4 in prostate cancer, identifying novel IRX4 transcripts and protein isoforms, shedding light on its potential role in PCa progression.
Article
Biochemistry & Molecular Biology
Sana Fatima, Swati Gupta, Abdul Burhan Khan, Sayeed Ur Rehman, Mohamad Aman Jairajpuri
Summary: Alpha-1-antichymotrypsin (ACT) is a protein that regulates the activity of proteases and is associated with diseases. Through bioinformatics and molecular biology, a novel isoform of ACT with a new N-terminus has been discovered, which lacks a signal sequence but retains activity. Additionally, a truncated transcript lacking certain structural elements has been identified, suggesting a potential non-inhibitory role. Further investigation is required to validate these findings.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Cell Biology
Weidi Wang, Yucan Chen, Jingjing Zhao, Liang Chen, Weichen Song, Li Li, Guan Ning Lin
Summary: The study explored the protein-protein interaction of NSD2 and its role in WHS and myeloma. Through immunoprecipitation mass spectrometry analysis, 890 isoform-specific PPI partners were identified, further divided into four categories of exon-specific interactome. The research revealed the diverse roles of NSD2 in RNA splicing processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Xiangyu Li, Woonghee Kim, Muhammad Arif, Chunxia Gao, Andreas Hober, David Kotol, Linnea Strandberg, Bjorn Forsstrom, Asa Sivertsson, Per Oksvold, Hasan Turkez, Morten Grotli, Yusuke Sato, Haruki Kume, Seishi Ogawa, Jan Boren, Jens Nielsen, Mathias Uhlen, Cheng Zhang, Adil Mardinoglu
Summary: Pyruvate kinase muscle type (PKM) is a key enzyme in glycolysis and plays an important role in cancer. The association between PKM expression and the survival outcome of patients with different cancers is controversial. System biology methods were employed to reveal the prognostic value and potential biological functions of PKM transcripts in different human cancers.
Article
Biology
Markus J. Sommer, Sooyoung Cha, Ales Varabyou, Natalia Rincon, Sukhwan Park, Ilia Minkin, Mihaela Pertea, Martin Steinegger, Steven L. Salzberg
Summary: The development of three-dimensional protein structure prediction methods has provided new opportunities for research on genomes and proteomes. By utilizing computational predictions of protein structures, it is possible to identify the functional protein product among multiple gene isoforms. In this study, we evaluated over 230,000 isoforms of human protein-coding genes using protein structure predictions, and identified several isoforms with more confidently predicted structures and potentially superior function compared to the canonical isoforms in the latest human gene database. We demonstrated the potential of protein structure prediction as a genome annotation tool and provided a resource of protein structures for better understanding the function of human genes and their isoforms.
Article
Virology
Amanda Westergren Jakobsson, Bo Segerman, Ola Wallerman, Sara Bergstrom Lind, Hongxing Zhao, Carl-Johan Rubin, Ulf Pettersson, Goran Akusjarvi
Summary: Utilizing the Nanopore long-read sequencing platform, we revealed the remarkable complexity of the human adenovirus type 2 transcriptome, identifying over 900 alternatively spliced mRNAs, with more than 850 being novel. The virus demonstrates a significant capacity to generate novel exon combinations, with the E3 region showing the highest complexity in late infection.
JOURNAL OF VIROLOGY
(2021)
Article
Endocrinology & Metabolism
Rene van Tienhoven, Maria J. L. Kracht, Arno R. van der Slik, Sofia Thomaidou, Anouk H. G. Wolters, Ben N. G. Giepmans, Juan Pablo Romero Riojas, Michael S. Nelson, Francoise Carlotti, Eelco J. P. de Koning, Rob C. Hoeben, Arnaud Zaldumbide, Bart O. Roep
Summary: Transcriptome analysis identified insulin-gene-derived transcripts in non-beta endocrine islet cells. Researchers studied alternative splicing of human INS mRNA in pancreatic islets and found an alternatively spliced INS product that is expressed in delta cells but not in beta cells. This variant encodes the complete insulin signal peptide and B chain, and its presence in delta cells may play a role in islet autoimmunity and pathology.
Article
Biochemistry & Molecular Biology
Lianlian Liu, Junlei Zhang, Jiaqi Wang, Yanping Tian, Jiali Wang, Yixiao Xu, Yuda Cheng, Meng Yu, Jiangjun Wang, Yi Yang, Xueyue Wang, Ran Yang, Wei Wu, Chen Zhang, Yan Hu, Rui Jian, Lan Xiao, Yan Ruan
Summary: In this study, 23 hYAP isoforms were identified in HEK293 cells, with 14 isoforms being reported for the first time. These isoforms were classified into hYAP-a and hYAP-b isoforms based on the variation in exon 1. The two groups of isoforms showed distinctly different subcellular localizations. hYAP-a isoforms could activate TEAD- or P73-mediated transcription, affect the proliferation rate, and enhance the cellular chemosensitivity of HEK293 cells. Moreover, different activation abilities and pro-cytotoxic effects were observed among hYAP-a isoforms. However, hYAP-b isoforms were not found to exert any significant biological effects. These findings contribute to a better understanding of the YAP gene structure and protein-coding capacity, and provide insights into the function and related molecular mechanisms of the Hippo-YAP signaling pathway.
Article
Biochemistry & Molecular Biology
Bernardo Bonilauri, Marlon D. M. Santos, Amanda Caroline Camillo-Andrade, Saloe Bispo, Fabio C. S. Nogueira, Paulo C. Carvalho, Nilson I. T. Zanchin, Juliana de S. da G. Fischer
Summary: The delay in blood-processing time directly impacts the proteomic profile of human PBMC, possibly through granulocyte contamination and activation.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2021)
Article
Microbiology
Ueriton Dias de Oliveira, Fred Luciano Neves Santos, Bernardo Galvao-Castro, Marco Aurelio Krieger, Nilson Ivo Tonin Zanchin
Summary: This study successfully produced recombinant antigenic proteins derived from HTLV-1 and HTLV-2, highlighting the strong potential of HTLV-1 antigens for serological diagnosis of HTLV-1 infections. However, there was a high level of cross-reaction between HTLV-1-positive samples and HTLV-2 antigens, which can be attributed to the sequence conservation between the structural proteins of these two closely related viruses.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Camila de Castro Ferezin, Fernanda Luisa Basei, Talita D. Melo-Hanchuk, Ana Luisa de Oliveira, Andressa Peres de Oliveira, Mateus P. Mori, Nadja C. de Souza-Pinto, Jorg Kobarg
Summary: NEK5 plays a role in regulating mitochondrial homeostasis and mtDNA maintenance, with its kinase activity being necessary for maintaining mitochondrial mass, functionality, and mtDNA integrity. The interaction between NEK5 and LonP1 may be crucial for these processes.
Review
Cell Biology
Isadora Carolina Betim Pavan, Andressa Peres de Oliveira, Pedro Rafael Firmino Dias, Fernanda Luisa Basei, Luidy Kazuo Issayama, Camila de Castro Ferezin, Fernando Riback Silva, Ana Luisa Rodrigues de Oliveira, Livia Alves dos Reis Moura, Mariana Bonjiorno Martins, Fernando Moreira Simabuco, Joerg Kobarg
Summary: NEKs are a family of Ser/Thr protein kinases that play important roles in cell cycle, mitosis, DNA damage response, and other biological functions in vertebrate cells. Research has primarily focused on their involvement in mitosis regulation and cell cycle, but recent studies have also shown their participation in DNA damage response pathways.
Article
Biochemistry & Molecular Biology
Gustavo Barbosa de Lima, Thaise Yasmine Vasconcelos de Lima Cavalcanti, Adriana Neuman Albuquerque Lins Moura de Brito, Ludmilla Arruda de Assis, Rafaela Paiva Andrade-Vieira, Eden Ribeiro Freire, Tatiana Reichert da Silva Assuncao, Christian Robson de Souza Reis, Nilson Ivo Tonin Zanchin, Beatriz Gomes Guimaraes, Osvaldo Pompilio de-Melo-Neto
Summary: This study investigated the interacting proteins of Leishmania EIF4E5, revealing its main interaction with EIF4G1 and other proteins. The study also explored the interactions of EIF4E5's C-terminal end and protein partners.
Article
Multidisciplinary Sciences
Arthur Schveitzer Ferreira, Amanda Lopacinski, Michel Batista, Priscila Mazzocchi Hiraiwa, Beatriz Gomes Guimaraes, Nilson Ivo Tonin Zanchin
Summary: Epidermal growth factors (EGF) play important roles in various aspects, including embryogenesis, skin development, and immune response homeostasis. However, recombinant production of these factors in prokaryotic systems is challenging due to their structural organization. This study presents a reliable method for producing seven human growth factors of the EGF family in Escherichia coli, demonstrating their folded and stable conformation and high activity at low concentrations.
SCIENTIFIC REPORTS
(2022)
Article
Infectious Diseases
Natalia Erdens Maron Freitas, Emily Ferreira Santos, Leonardo Maia Leony, Angelo Antonio Oliveira Silva, Ramona Tavares Daltro, Larissa de Carvalho Medrado Vasconcelos, Gabriela Agra Duarte, Cristiane Oliveira da Mota, Edimilson Domingos Silva, Paola Alejandra Fiorani Celedon, Nilson Ivo Tonin Zanchin, Fred Luciano Neves Santos
Summary: The chimeric antigens IBMP-8.1, IBMP-8.2, IBMP-8.3, and IBMP-8.4 were evaluated in the double-antigen sandwich ELISA platform. The diagnostic performance of the DAgS-ELISA was promising, but improvements are being considered to increase its sensitivity.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Medicine, General & Internal
Emily Ferreira dos Santos, angelo Antonio Oliveira Silva, Natalia Erdens Maron Freitas, Leonardo Maia Leony, Ramona Tavares Daltro, Carlos Antonio de Souza Teles Santos, Maria da Conceicao Chagas de Almeida, Fernando Luiz Vieira de Araujo, Paola Alejandra Fiorani Celedon, Marco Aurelio Krieger, Nilson Ivo Tonin Zanchin, Mitermayer Galvao dos Reis, Fred Luciano Neves Santos
Summary: Chagas disease (CD) is a major cause of inability to donate blood. The current blood screening methods for anti-Trypanosoma cruzi antibodies have high false positive rates. A research group has developed four chimeric proteins that have shown high performance and low cross-reactivity rates. These proteins can be used to screen for CD in blood donations, reducing the risk of unnecessary blood disposal or T. cruzi transmission.
FRONTIERS IN MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Arthur Schveitzer Ferreira, Amanda Lopacinski, Michel Batista, Priscila Mazzocchi Hiraiwa, Natalia Fernanda Bueno, Beatriz Gomes Guimaraes, Nilson I. T. Zanchin
Summary: NRG1 is a growth factor family involved in signaling pathways of various normal cell types and human diseases. In this study, the hNRG1 alpha EGF domain was successfully expressed and purified in E. coli, demonstrating its high activity in cell proliferation and migration.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Giovanna Cesaro, Heloisa Tramontin da Soler, Eloise Pavao Guerra-Slompo, Ahmed Haouz, Pierre Legrand, Nilson Ivo Tonin Zanchin, Beatriz Gomes Guimaraes
Summary: Rrp44/Dis3 is a conserved eukaryotic ribonuclease that plays a role in processing and degradation of almost all types of RNA. Depletion of Rrp44 in Trypanosoma brucei blocks maturation of ribosomal RNA, leading to disruption of ribosome synthesis and inhibition of cell proliferation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Eloise Pavao Guerra-Slompo, Giovanna Cesaro, Beatriz Gomes Guimaraes, Nilson Ivo Tonin Zanchin
Summary: Trypanosoma brucei, a protozoan with fragmented large subunit rRNA, requires additional processing for the maturation of its LSU rRNA. TbRRP44, a nuclease, is essential for this maturation process, where its RNB domain and physical presence of the PIN domain play crucial roles. A new endonucleolytic cleavage site was identified in ITS1, and TbRRP44 is also involved in the degradation of 5'-ETS and part of ITS1 during the maturation of 18S rRNA 3'-end.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Infectious Diseases
Ramona Tavares Daltro, Emily Ferreira Santos, Angelo Antonio Oliveira Silva, Natalia Erdens Maron Freitas, Leonardo Maia Leony, Larissa Carvalho Medrado Vasconcelos, Alejandro Ostermayer Luquetti, Paola Alejandra Fiorani Celedon, Nilson Ivo Tonin Zanchin, Carlos Gustavo Regis-Silva, Fred Luciano Neves Santos
Summary: This study evaluated the diagnostic potential of four chimeric recombinant antigens for diagnosing chronic Chagas disease. The results showed that these antigens can effectively discriminate between T. cruzi-positive and -negative samples.
PLOS NEGLECTED TROPICAL DISEASES
(2022)
Article
Cell Biology
Isadora Carolina Betim Pavan, Fernanda Luisa Basei, Matheus Brandemarte Severino, Ivan Rosa e Silva, Luidy Kazuo Issayama, Mariana Camargo Silva Mancini, Mariana Marcela Gois, Luiz Guilherme Salvino da Silva, Rosangela Maria Neves Bezerra, Fernando Moreira Simabuco, Jorg Kobarg
Summary: NEK6 is a central kinase in developing castration-resistant prostate cancer (CRPC), but the pathways it regulates are unclear. This study found that knocking out NEK6 decreased cell viability, mitochondrial activity, and antioxidant defenses, while increasing intracellular ROS levels, JNK phosphorylation, and DNA damage markers. Exogenous overexpression of NEK6 had the opposite effects. NEK6 also played a role in cell death, cisplatin sensitivity, and nuclear localization of NF-kappa B2. These findings suggest that NEK6 inhibition may be a new therapeutic strategy for CRPC.
Article
Biochemical Research Methods
Eloise Pavao Guerra-Slompo, Gisele Fernanda Assine Picchi-Constante, Martin Marek, Christophe Romier, Wolfgang Sippl, Nilson Ivo Tonin Zanchin
Summary: We present a combined in cellulo and in vivo approach to identify compounds with high potential for inhibiting Trypanosoma cruzi. The in cellulo assays consist of two phases - one for excluding inactive or toxic compounds and the other for determining IC50, CC50, and selective index (SI). Compounds with high SI are further tested in in vivo infection models to evaluate their efficacy compared to benznidazole, a reference drug for Chagas disease treatment. For more details, refer to Marek et al. (2021).
Article
Biochemical Research Methods
Gisele Fernanda Assine Picchi-Constante, Priscila Mazzocchi Hiraiwa, Martin Marek, Vanessa Zulkievicz Rogerio, Eloise Pavao Guerra-Slompo, Christophe Romier, Nilson Ivo Tonin Zanchin
Summary: This study presents a novel genetic complementation strategy for investigating gene function in Trypanosoma cruzi, the parasite responsible for Chagas disease. By combining CRISPR-Cas9 technology with recombination of resistant variants of the target gene containing desired mutations, detailed exploration of protein function is made possible. This experimental approach overcomes some of the limitations associated with traditional gene knockouts in T. cruzi.