Review
Cell Biology
John G. Conboy
Summary: Deep intron elements play crucial roles in regulating splicing processes, such as recursive splicing exons, decoy splice sites, and RNA:RNA bridges, with mutations potentially leading to human diseases. Understanding these noncanonical splicing pathways and regulatory signals in deep introns is important for medical applications and uncovering new disease mechanisms.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2021)
Review
Immunology
Jianli Zhou, Qiao Zhang, Yuzhen Zhao, Yuchen Song, Yanan Leng, Moxian Chen, Shaoming Zhou, Zhaoxia Wang
Summary: Inflammatory bowel disease (IBD) is a group of chronic diseases including Crohn's disease and ulcerative colitis, which have a global impact on both children and adults. The burden of IBD is increasing worldwide, and the costs associated with it are high. The pathogenesis of IBD is still unclear, but is believed to be related to environmental factors, gut microbiota, immune imbalance, and genetic susceptibility. This article reviews the research progress on alternative splicing events, splicing factors, and splicing mutations associated with IBD.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jamal Elhasnaoui, Giulio Ferrero, Valentina Miano, Lorenzo Franchitti, Isabella Tarulli, Lucia Coscujuela Tarrero, Santina Cutrupi, Michele De Bortoli
Summary: This study found that ESRP1 is overexpressed in breast cancer patients, particularly in luminal BCs, and is correlated with estrogen receptor alpha levels. Analysis of genome-binding profiles revealed that ER alpha regulates the expression of ESRP1 and ESRP2 genes. Knocking down ESRP1/2 led to dysregulation of 754 genes, including alterations in alternative splicing events involved in cell signaling, metabolism, cell growth, and EMT. Functional network analysis identified RAC1 as the hub node affected by ESRP1/2 silencing in ER alpha+ BCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Xiaoli Jin
Summary: Serine/arginine-rich (SR) proteins play important roles in plant growth and development, signal transduction, and response to biotic and abiotic stresses. They function under a complex regulatory network and participate in various cellular processes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Walter Santana-Garcia, Jaime A. Castro-Mondragon, Monica Padilla-Galvez, Nga Thi Thuy Nguyen, Ana Elizondo-Salas, Najla Ksouri, Francois Gerbes, Denis Thieffry, Pierre Vincens, Bruno Contreras-Moreira, Jacques van Helden, Morgane Thomas-Chollier, Alejandra Medina-Rivera
Summary: RSAT is a suite of tools that enables the detection and analysis of cis-regulatory elements in genomic sequences. It offers multiple modes of access and supports a wide range of genomes, catering to the needs of different biological communities.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Yunqi Chao, Yonghui Jiang, Mianling Zhong, Kaiyan Wei, Chenxi Hu, Yifang Qin, Yiming Zuo, Lili Yang, Zheng Shen, Chaochun Zou
Summary: Alternative splicing plays a crucial role in regulating gene expression patterns post-transcriptionally, particularly in adipogenesis. Aberrant expression and alterations in splicing regulators are linked to mutations in obesity-related genes, indicating their potential role in diet-induced obesity and metabolic dysregulation. Research on the splicing machinery's interaction with obesity and metabolic disorders provides insights for potential therapeutic strategies in clinical settings.
CELL AND BIOSCIENCE
(2021)
Article
Engineering, Environmental
Bing Gong, Erkai He, Cornelis A. M. Van Gestel, Yetao Tang, Wenjun Yang, Jing Yang, Ye Li, Hao Qiu
Summary: The mixture toxicity and interaction of La-Ce mixtures on Enchytraeus crypticus increased over time, with antagonistic effects observed after 1 to 2 days and additive effects thereafter. The TK-TD model revealed the interactions between La and Ce in terms of uptake, elimination, and toxicity, showing that competition effects led to reduced toxicity.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Philipp Keyl, Philip Bischoff, Gabriel Dernbach, Michael Bockmayr, Rebecca Fritz, David Horst, Nils Bluethgen, Gregoire Montavon, Klaus-Robert Mueller, Frederick Klauschen
Summary: The molecular heterogeneity of cancer cells contributes to the often partial response to targeted therapies and relapse of disease due to the escape of resistant cell populations. Single-cell sequencing has limitations in understanding this heterogeneity, and scGeneRAI is an explainable deep learning approach that can infer gene regulatory networks from single-cell RNA sequencing data to provide functional insights. Our method reveals characteristic network patterns for tumor cells and normal epithelial cells and allows the reconstruction of networks at the level of single cells, which helps characterize the heterogeneity of gene regulation within and across tumors.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Peng Zhou, Tara A. Enders, Zachary A. Myers, Erika Magnusson, Peter A. Crisp, Jaclyn M. Noshay, Fabio Gomez-Cano, Zhikai Liang, Erich Grotewold, Kathleen Greenham, Nathan M. Springer
Summary: Changes in gene expression are crucial for responses to abiotic stress. Transcriptome profiling of heat- or cold-stressed maize genotypes reveals many alterations in transcript abundance. By analyzing expression responses in multiple genotypes and identifying cis- or trans-regulatory variation, predictive models of gene expression responses for thermal stress-responsive genes can be developed. Models focusing on unmethylated regions near the transcription start sites (TSSs) show improved accuracy, suggesting that different genes may have varying response dynamics to stress.
Article
Biotechnology & Applied Microbiology
Qiuying Ding, Zhengping Hou, Zhibo Zhao, Yao Chen, Lei Zhao, Yue Xiang
Summary: In this study, a prognostic signature reflecting genomic instability and overall survival (OS) of colorectal cancer (CRC) patients was constructed by analyzing splicing profiles, somatic mutations, and other related information. This signature showed good predictive performance for OS and could be used for clinical stratification and prognosis prediction. The study also identified splicing factors associated with OS and verified their roles in cell proliferation and migration.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Yu-jia Zhao, Lin-Yong Wu, Jin-shu Pang, Wei Liao, Yu-ji Chen, Yun He, Hong Yang
Summary: This study comprehensively investigated the genomic and epigenomic characteristics of SFs in HCC, revealing several clinically relevant SFs that could serve as effective biomarkers for monitoring the onset and prognosis of HCC. Copy number variation was found to be common in HCC, and the complex expression regulation of SFs was significantly affected by copy number variant and methylation. Furthermore, a potential regulatory network of SFs was identified, shedding light on their mechanisms in regulating clinically relevant alternative splicing events in HCC.
Article
Endocrinology & Metabolism
Shi-meng Guo, Xing-ping Liu, Qing Tian, Cai-feng Fei, Yi-ran Zhang, Zhi-ming Li, Ying Yin, Ximiao He, Li-quan Zhou
Summary: This study reveals the importance of alternative splicing at Ezh2 exon 3 in mouse oocyte development. Ezh2(Short) female mice exhibit decreased fertility and obstructed oogenesis with compromised mitochondrial function in their oocytes.
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY
(2022)
Article
Computer Science, Artificial Intelligence
Jinbo Xu, Matthew McPartlon, Jin Li
Summary: Recent advances in computational protein structure prediction have shown significant improvements by integrating deep learning and co-evolutionary analysis. Using ResNet, predictions of correct protein folds have been successful even without co-evolution information, suggesting potential for learning important protein sequence-structure relationships.
NATURE MACHINE INTELLIGENCE
(2021)
Article
Biotechnology & Applied Microbiology
Kurtis Stefan, Artem Barski
Summary: Cis-regulatory elements (CRE) are essential for coordinating gene expression programs in specific cells. The STARR-Seq technique has been used to annotate functional CREs, but is mostly limited to cell lines. In this study, Lenti-STARR-Seq was successfully implemented in human CD4+ T cells, providing a genome-wide analysis of CRE function in primary cells. The study identified thousands of enhancers and negative regulatory elements (NREs) in CD4+ T cells, and revealed differences in nucleosome organization between enhancers and NREs. The findings also support the concept of silencer repurposing as enhancers in alternate cell types.
Article
Biotechnology & Applied Microbiology
Yongil Yang, Jun Hyung Lee, Magen R. Poindexter, Yuanhua Shao, Wusheng Liu, Scott C. Lenaghan, Amir H. Ahkami, Eduardo Blumwald, Charles Neal Stewart
Summary: Researchers identified five synthetic promoters in hybrid poplar that showed better inducibility under abiotic stress conditions compared to native promoters, demonstrating the potential of synthetic biology in producing transgenic plants with improved stress resistance traits.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Article
Genetics & Heredity
Kandai Nozu, Yoshimi Nozu, Keita Nakanishi, Takao Konomoto, Tomoko Horinouchi, Akemi Shono, Naoya Morisada, Shogo Minamikawa, Tomohiko Yamamura, Junya Fujimura, Koichi Nakanishi, Takeshi Ninchoji, Hiroshi Kaito, Ichiro Morioka, Mariko Taniguchi-Ikeda, Igor Vorechovsky, Kazumoto Iijima
JOURNAL OF HUMAN GENETICS
(2017)
Article
Biochemistry & Molecular Biology
Jana Kralovicova, Igor Vorechovsky
NUCLEIC ACIDS RESEARCH
(2017)
Article
Biochemistry & Molecular Biology
Li Chen, Robert Weinmeister, Jana Kralovicova, Lucy P. Eperon, Igor Vorechovsky, Andrew J. Hudson, Ian C. Eperon
NUCLEIC ACIDS RESEARCH
(2017)
Article
Genetics & Heredity
Kandai Nozu, Shogo Minamikawa, Shiro Yamada, Masafumi Oka, Motoko Yanagita, Naoya Morisada, Shuichiro Fujinaga, China Nagano, Yoshimitsu Gotoh, Eihiko Takahashi, Takahiro Morishita, Tomohiko Yamamura, Takeshi Ninchoji, Hiroshi Kaito, Ichiro Morioka, Koichi Nakanishi, Igor Vorechovsky, Kazumoto Iijima
JOURNAL OF HUMAN GENETICS
(2017)
Article
Genetics & Heredity
Kandai Nozu, Kazumoto Iijima, Toru Igarashi, Shiro Yamada, Jana Kralovicova, Yoshimi Nozu, Tomohiko Yamamura, Shogo Minamikawa, Ichiro Morioka, Takeshi Ninchoji, Hiroshi Kaito, Koichi Nakanishi, Igor Vorechovsky
MOLECULAR GENETICS & GENOMIC MEDICINE
(2017)
Article
Biochemistry & Molecular Biology
Jana Kralovicova, Ivana Sevcikova, Eva Stejskalova, Mina Obuca, Michael Hiller, David Stanek, Igor Vorechovsky
NUCLEIC ACIDS RESEARCH
(2018)
Article
Medicine, Research & Experimental
Ana Lages, Christopher G. Proud, John W. Holloway, Igor Vorechovsky
MOLECULAR THERAPY-NUCLEIC ACIDS
(2019)
Article
Oncology
Jana Kralovicova, Ivana Borovska, Monika Kubickova, Peter J. Lukavsky, Igor Vorechovsky
Article
Biochemistry & Molecular Biology
Maria Elena Vilar Alvarez, Martin Chivers, Ivana Borovska, Steven Monger, Eleni Giannoulatou, Jana Kralovicova, Igor Vorechovsky
Summary: TEs play a crucial role in shaping the evolution of exon-intron structure and have been linked to morbidity. This study investigates how recent TE invasions cooperate with older TEs in generating new coding sequences, identifying novel TE clusters that facilitate exon selection. By analyzing the RNA secondary structure and functional impact of mutations in exon-intron boundaries, the study sheds light on the formation and kinetics of pre-mRNA building blocks necessary for splice-site selection. The findings provide valuable insights into the fine-tuning of auxiliary splicing motifs and the regulation of aberrant splice-site activation.
Article
Biochemistry & Molecular Biology
Jana Kralovicova, Ivana Borovska, Reuben Pengelly, Eunice Lee, Pavel Abaffy, Radek Sindelka, Frank Grutzner, Igor Vorechovsky
Summary: The study reveals the mechanism by which Ca2+-sensitive and insensitive E1 subunits regulate tissue-specific NADH and ATP supply through different exons. Remote lariat branch points restrict intron length and prevent transposon insertions, with the expansion of dBPs in early terrestrial species.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
D. Alexieva, Y. Long, R. Sarkar, H. Dhayan, E. Bruet, Rm Winston, I Vorechovsky, L. Castellano, N. J. Dibb
Summary: Mutations of splice sites, auxiliary splicing elements, and the splicing machinery can cause a wide range of genetic diseases. Background splicing information can predict the complex effects of splice mutations, including cryptic splice activation and single or multiple exon skipping. Comparison of known background splicing information with human splice site mutation databases can effectively predict the impact of splice site mutations.
Article
Biochemistry & Molecular Biology
Reuben J. Pengelly, Dara Bakhtiar, Ivana Borovska, Jana Kralovicova, Igor Vorechovsky
Summary: Auxilliary splicing sequences in exons, known as enhancers (ESEs) and silencers (ESSs), have undergone strong selection pressures. The exonic sequences encoding calcium-binding residues show higher levels of exon inclusion, indicating their high retention capacity during eukaryotic evolution.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Neurosciences
Igor Vorechovsky
Summary: Olduvai protein domains have experienced the greatest increase in copy number of any coding region in the human genome and are associated with brain volume, neuron count, cognitive abilities, and disorders of the autistic spectrum. Research shows that the inclusion of Olduvai exon doublets in mature transcripts is facilitated by a potent splicing enhancer created through duplication within the first exon, safeguarding the expanded Olduvai exon doublets in the mature transcriptome.
Article
Biochemistry & Molecular Biology
Ivana Borovska, Igor Vorechovsky, Jana Kralovicova
Summary: Transcriptomic diversity in primates was expanded by exonizations of intronic Alu elements. RNA conformation changes rather than splicing regulatory motifs were found to better predict the splicing outcome. SRP9/14 heterodimer was shown to be involved in the splicing regulation of Alu-derived exons. Nucleotide substitutions during primate evolution relaxed the conserved left-arm AluJ structure and reduced the capacity of SRP9/14 to stabilize the closed Alu conformation.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Dara Bakhtiar, Katarina Vondraskova, Reuben J. Pengelly, Martin Chivers, Jana Kralovicova, Igor Vorechovsky
Summary: This study investigates the splicing codes of human exons encoding two essential divalent metals. The results show that exons encoding Zn2+-coordinating amino acids are less supported by auxiliary splicing motifs compared to exons coordinating Ca2+, but are compensated by other mechanisms to ensure sufficient splicing and metalloprotein expression.
NUCLEIC ACIDS RESEARCH
(2023)