Article
Veterinary Sciences
Junfeng Zhan, Jianbo Li, Yuerong Wu, Panfeng Wu, Ziqi Yu, Peng Cui, Mofan Zhou, Yumin Xu, Tingyu Jin, Ziye Du, Mengcheng Luo, Cong Liu
Summary: Sugp2 is a chromatin-associated candidate protein that plays a role in spermatogenesis. Depletion of Sugp2 by CRISPER-Cas9 technology revealed that it controls a network of genes related to metal ion and ATP binding.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Di Wu, Faheem Ahmed Khan, Lijun Huo, Fei Sun, Chunjie Huang
Summary: Infertility is a serious global health issue with significant socio-economic impacts, predominantly caused by male factors. The post-transcriptional gene regulation mechanisms of alternative splicing and miRNA-mediated RNA silencing play crucial roles in male infertility, and paternal inputs such as unhealthy lifestyle can influence offspring through miRNA-mediated epigenetic inheritance.
Article
Medicine, Research & Experimental
Song Zhu, Weiping Chen, Jizhong Wang, Ling Qi, Huilin Pan, Zhengfu Feng, Dongbo Tian
Summary: The protein SAM68 plays a crucial role in promoting tumorigenesis and metastasis of lung adenocarcinoma cells by regulating the metabolic switch to glycolysis. Higher levels of SAM68 expression in LUAD patients were associated with increased tumor recurrence, lower recurrence-free survival, higher cancer-related death risk, and shorter overall survival. SAM68 functions by mediating alternative splicing of PKM pre-mRNAs to enhance the formation of the oncogenic PKM2 isoform, driving aerobic glycolysis and tumor progression. Targeting SAM68 could be a promising therapeutic approach for LUAD treatment.
Review
Biochemistry & Molecular Biology
Xiaoli Wang, Lisha Yin, Yujiao Wen, Shuiqiao Yuan
Summary: Mitochondria adjust their morphology to suit different cell types and environments, playing important roles in spermatogenesis. Deficiencies in mitochondria can cause male infertility and regulate piRNA biogenesis. This review describes the characteristics of mitochondria, focusing on key mitochondrial factors and the underlying molecular mechanisms in spermatogenesis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Gabriella Chieffi Baccari, Giuseppe Iurato, Alessandra Santillo, Brian Dale
Summary: Male infertility is correlated with the shortening of sperm telomeres, which regulate the reproductive lifespan. Telomeres are composed of DNA repeats and are coupled to proteins and RNA. Telomerase activity in male germ cells maintains telomere length during spermatogenesis, despite DNA replication and genotoxic factors. Exposure to pollutants has been associated with male infertility, but few consider telomeric DNA as a parameter for sperm function. This review aims to provide comprehensive data on the structure and function of telomeres in spermatogenesis and the influence of environmental pollutants.
Article
Biochemistry & Molecular Biology
Idir Malki, Inara Liepina, Nora Kogelnik, Hollie Watmuff, Sue Robinson, Adam Lightfoot, Oksana Gonchar, Andrew Bottrill, Andrew M. Fry, Cyril Dominguez
Summary: In this study, we comprehensively investigated the post-translational modifications of Sam68 protein at different stages of the cell cycle using mass spectrometry, nuclear magnetic resonance spectroscopy, and cell biology techniques. We found that Sam68 is specifically phosphorylated at T33 and T371 by Cdk1, which reduces its RNA binding ability, controls its cellular localization, and decreases its alternative splicing activity.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Cell Biology
Masaki Kawase, Kenji Ichiyanagi
Summary: In mammals, germ cells produce small regulatory RNAs called piRNAs, which have different characteristics and expression dynamics during development. The length of piRNAs is correlated with PIWI-like proteins, and retrotransposon-derived piRNAs are abundantly produced but decline in abundance as development proceeds.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Plant Sciences
Ibtissam Jabre, Saurabh Chaudhary, Wenbin Guo, Maria Kalyna, Anireddy S. N. Reddy, Weizhong Chen, Runxuan Zhang, Cornelia Wilson, Naeem H. Syed
Summary: Research suggests that nucleosome positioning affects cold-induced alternative splicing in plants. In Arabidopsis thaliana, different types of alternative splicing events are closely linked to characteristic nucleosome occupancy levels. Internal regions of protein-coding exons, known as exitrons, exhibit distinct nucleosome positioning patterns compared to other alternatively spliced regions.
Article
Plant Sciences
Ibtissam Jabre, Saurabh Chaudhary, Cornelia M. Wilson, Dorothee Staiger, Naeem Syed
Summary: Plants utilize gene regulatory mechanisms to adapt to environmental challenges. This study reveals that stochastic changes in DNA methylation can modulate nucleosome occupancy and alternative splicing (AS) in response to cold stress, thus influencing plant metabolism and stress adaptation.
Article
Cell Biology
Lindy Jensen, Zsolt G. Venkei, George J. Watase, Bitarka Bisai, Scott Pletcher, Cheng-Yu Lee, Yukiko M. Yamashita
Summary: The translational regulator me31B plays a critical role in preventing excess dedifferentiation in the Drosophila male germline, leading to spermatogonia dedifferentiating into germline stem cells (GSCs) at a dramatically elevated frequency in its absence. The excess dedifferentiation is likely due to misregulation of nos, a key regulator of germ cell identity and GSC maintenance. These findings reveal negative regulation of dedifferentiation to balance stem cell maintenance with differentiation.
JOURNAL OF CELL SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Verena Hoeffken, Sara Di Persio, Sandra Laurentino, Margot J. Wyrwoll, Nicole Terwort, Anke Hermann, Albrecht Roepke, Manon S. Oud, Joachim Wistuba, Sabine Kliesch, Hermann J. Pavenstaedt, Frank Tuettelmann, Nina Neuhaus, Joachim Kremerskothen
Summary: The WWC protein family regulates cell proliferation and organ growth control via the Hippo signaling pathway. WWC2 has a relatively high expression in the testis and is associated with spermatogenesis and male fertility. Rare variants of the WWC2 gene may be linked to male infertility.
Article
Cell Biology
Maira S. Rodrigues, Aldo Tovo-Neto, Ivana F. Rosa, Lucas B. Doretto, Hamideh P. Fallah, Hamid R. Habibi, Rafael H. Nobrega
Summary: Thyroid hormones play a critical role in controlling various physiological processes in vertebrates, including development, growth, and metabolism. This study investigates the effects of methimazole-induced hypothyroidism on testicular function in adult zebrafish. The results demonstrate that the inhibition of thyroid hormone significantly alters spermatogenesis and decreases the number of spermatozoa in zebrafish. Moreover, the study suggests that thyroid hormones not only affect the brain-pituitary-peripheral axis but also exert a direct action on the testis. These findings indicate the essential role of thyroid hormones in the multifactorial control of reproduction and testicular function in zebrafish and possibly other vertebrate species.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Environmental Sciences
Won-Young Lee, Hyun-Jung Park
Summary: T-2 toxin induces reproductive toxicity and germ cell damage. It reduces testicular germ cell number and downregulates their corresponding markers, but increases Sertoli cell markers and steroidogenic enzyme expression. T-2 toxin also decreases cell viability, increases apoptosis, and triggers ROS-mediated JNK/p38-MAPK signaling pathway, leading to mitochondrial dysfunction and apoptotic cell death in germ cells.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2023)
Article
Agriculture, Dairy & Animal Science
Changhua Sun, Kai Jin, Qisheng Zuo, Hongyan Sun, Jiuzhou Song, Yani Zhang, Guohong Chen, Bichun Li
Summary: This study investigated alternative splicing (AS) events during chicken germ cell development and identified crucial stage-specific genes through RNA-seq data analysis. The results provide a theoretical foundation for further analysis of the regulation mechanism of key genes involved in germ cell formation. Our findings may contribute to improving treatment options for male infertility in the future.
Review
Biochemistry & Molecular Biology
Carol Imbriano, Silvia Belluti
Summary: Alternative splicing (AS) is a tightly regulated mechanism that generates the complex human proteome from a small number of genes. Histone modifications and variants can affect splicing outcomes, and dysregulation of the splicing code may contribute to cancer development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Lidia Chellini, Marco Pieraccioli, Claudio Sette, Maria Paola Paronetto
Summary: DHX9 plays an important role in the development of prostate cancer, with up-regulation of DHX9 correlating with advanced stage and poor prognosis. The limited treatment options for patients in the castration-resistant stage make DHX9 a potential new druggable target.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Veronica Verdile, Francesca Svetoni, Piergiorgio La Rosa, Gabriele Ferrante, Eleonora Cesari, Claudio Sette, Maria Paola Paronetto
Summary: Alternative splicing is a crucial regulatory process for amplifying genomic information and expanding proteomic diversity, particularly in the brain. This study identifies the Ewing sarcoma protein (EWS) as a novel player in alternative splicing regulation during neuronal differentiation. EWS depletion in neuronal progenitor cells leads to premature differentiation and global changes in splicing regulation. EWS controls the alternative splicing of various genes, including the pivotal transcription factor FOXP1, contributing to the switch of gene expression underlying neuronal differentiation.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Oncology
Claudio Sette, Maria Paola Paronetto
Summary: High throughput exome sequencing has revealed recurrent cancer-associated mutations in spliceosomal components, which promote tumor phenotype and make cancer cells vulnerable to splicing-targeting approaches. Thus, understanding the mechanisms and roles of abnormal splicing in tumor metabolism could lead to the development of novel tumor-targeting drugs.
Article
Oncology
Ramona Palombo, Maria Paola Paronetto
Summary: This study demonstrates that etoposide can inhibit the expression of the CCND1 gene in Ewing sarcoma by promoting the transcription of a promoter-associated noncoding RNA (pncCCND1_B) and forming a molecular complex with Sam68 and DHX9. The inhibition of CCND1 expression is accompanied by epigenetic changes and the formation of DNA: RNA hybrids. This finding provides insights into the mechanism of Ewing sarcoma treatment.
Article
Oncology
Ramona Palombo, Ilaria Passacantilli, Francesca Terracciano, Alessia Capone, Alessandro Matteocci, Simon Tournier, Antonio Alberdi, Valerio Chiurchiu, Elisabetta Volpe, Maria Paola Paronetto
Summary: In this study, the researchers identified ATF3 as a key mediator of the PI3K/AKT/mTOR pathway in Ewing sarcoma cells. ATF3 promotes tumor growth and metastasis by modulating the expression of chemokine-encoding genes, including CXCL8. This study provides valuable insights into the chemokine signaling in Ewing sarcoma and suggests that targeting the PI3K/AKT/mTOR pathway could promote an anti-tumoral immune response.
Article
Multidisciplinary Sciences
Esley Torres-Garcia, Raul Pinto-Camara, Alejandro Linares, Damian Martinez, Victor Abonza, Eduardo Brito-Alarcon, Carlos Calcines-Cruz, Gustavo Valdes-Galindo, David Torres, Martina Jablonski, Hector H. Torres-Martinez, Jose L. Martinez, Haydee O. Hernandez, Jose P. Ocelotl-Oviedo, Yasel Garces, Marco Barchi, Rocco D'Antuono, Ana Boskovic, Joseph G. Dubrovsky, Alberto Darszon, Mariano G. Buffone, Roberto Rodriguez Morales, Juan Manuel Rendon-Mancha, Christopher D. Wood, Armando Hernandez-Garcia, Diego Krapf, Alvaro H. Crevenna, Adan Guerrero
Summary: This study presents a new super-resolution microscopy algorithm called Mean-Shift Super Resolution (MSSR), which extends the spatial resolution of single fluorescence images beyond the diffraction limit. MSSR works on various fluorophore densities and optical setups, and has denoising capabilities.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Teresa Giannattasio, Erika Testa, Ramona Palombo, Lidia Chellini, Flavia Franceschini, Alvaro Crevenna, Petko M. Petkov, Maria Paola Paronetto, Marco Barchi
Summary: In mammals, meiotic recombination is initiated by the introduction of DNA double strand breaks (DSBs) into narrow segments of the genome, defined as hotspots, which is carried out by the SPO11/TOPOVIBL complex. PRDM9 plays a major role in specifying hotspots by generating trimethylation on specific lysine residues of histone H3. Recently, FUS/TLS has been found to interact with PRDM9 and REC114, suggesting that it is a component of the protein complex involved in meiotic recombination initiation. Furthermore, FUS/TLS is localized at H3K4me3-marked hotspots and the pseudo-autosomal region.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Valentina Panzeri, Marco Pieraccioli, Eleonora Cesari, Pierre de la Grange, Claudio Sette
Summary: Transcription-associated cyclin-dependent kinases (CDKs) regulate the transcription cycle through phosphorylation of RNA polymerase II (RNAPII). This study found that inhibiting CDK12 and CDK13 impaired splicing of specific promoter-proximal introns. The inhibition of CDK12/13 disrupted the interaction between SF3B1 and RNAPII, resulting in retention of these introns and a synergistic effect with another inhibitor on cell survival and cancer progression.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Psychiatry
Marika Guerra, Vanessa Medici, Robert Weatheritt, Valentina Corvino, Daniela Palacios, Maria Concetta Geloso, Donatella Farini, Claudio Sette
Summary: Autism spectrum disorder (ASD) is a highly heritable neurodevelopmental syndrome characterized by social and communication impairment, repetitive behavior, and intellectual disability. Despite the association of multiple genes with ASD, most patients do not have detectable genetic alterations, suggesting the involvement of environmental factors. Transcriptome analysis reveals distinct gene expression patterns in autistic brains, providing insight into the mechanisms underlying the effects of genetic and environmental factors. A study focusing on the cerebellum, a brain area strongly associated with ASD, identifies a coordinated and temporally regulated gene expression program during postnatal development, enriched in ASD-linked genes. Dysregulation of these genes in the developing cerebellum of an ASD mouse model correlates with impaired social behavior and altered cerebellar morphology. The findings highlight the importance of understanding the complex transcriptional program related to ASD in cerebellar development and the dysregulation of genes in this brain area.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Biochemistry & Molecular Biology
Veronica Verdile, Veronica Riccioni, Marika Guerra, Gabriele Ferrante, Claudio Sette, Cristiana Valle, Alberto Ferri, Maria Paola Paronetto
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of motor neurons, leading to paralysis and death. Dysregulation of synaptic structure and function has been identified as a pathogenic feature of ALS. Alternative pre-mRNA splicing (AS) is associated with synapse formation and functional specification and exploring its link with ALS could lead to new therapeutic opportunities.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Teresa Giannattasio, Erika Testa, Monica Faieta, Matteo Lampitto, Daniela Nardozi, Stefano di Cecca, Antonella Russo, Marco Barchi
Summary: XY chromosome missegregation is common in humans and can lead to sterility or the generation of aneuploid spermatozoa. This study investigates the lack of double-strand breaks (DSBs) in the pseudoautosomal region (PAR) as a leading cause of XY missegregation in mice. The study demonstrates that the genetic background of mice affects the length of chromatin loops in the PAR and the proficiency of XY recombination. The findings suggest that varying expression of Spo11 splice isoforms can recover XY recombination and synapsis.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Oncology
Valentina Frezza, Lidia Chellini, Arianna Del Verme, Maria Paola Paronetto
Summary: Recent evidence has shown that RNA editing, in addition to somatic mutations and alternative splicing changes, plays a significant role in altering genetic information in a dynamic fashion. This form of post-transcriptional RNA modification is closely associated with the development of various human diseases, including cancer, by regulating various cellular processes. Studies on the impact of RNA editing in cancer transformation are gaining increasing interest, particularly in relation to cell proliferation, differentiation, invasion, stemness, and drug resistance.
Article
Biochemistry & Molecular Biology
Lidia Chellini, Marzia Scarfo, Davide Bonvissuto, Claudio Sette, Maria Paola Paronetto
Summary: In this study, researchers found that the DHX9/KDM2B complex can serve as a new drug target for treating aggressive Ewing sarcoma. By regulating the expression of the Hippo pathway regulator YAP1, this complex can influence the oncogenic properties of Ewing sarcoma cells.