Article
Multidisciplinary Sciences
Huijuan Feng, Daniel F. Moakley, Shuonan Chen, Melissa G. McKenzie, Vilas Menon, Chaolin Zhang
Summary: The study reveals distinct splicing programs between glutamatergic and GABAergic neurons, as well as between subclasses within each neuronal class, showing differential splicing at multiple hierarchical levels. The results suggest graded regulation of alternative splicing across neuronal cell types, providing a mechanism to specify neuronal identity and function orthogonal to transcriptional regulation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Qiang Sun, Ye Han, Jianxing He, Jie Wang, Xuejie Ma, Qianqian Ning, Qing Zhao, Qian Jin, Lili Yang, Shuang Li, Yang Li, Qiaoming Zhi, Junnian Zheng, Dong Dong
Summary: This study investigates the transcriptome complexity in colorectal cancer (CRC) using long-read sequencing technology and short-read RNA-seq methods. A novel splicing isoform, TIMP1 ?4-5, is identified and its ectopic expression is found to suppress tumor cell growth and metastasis. Furthermore, a CRISPR/dCasRx-based strategy is introduced to induce TIMP1 exon 4-5 exclusion, which has the potential to restrain CRC growth.
Article
Biology
Vita Setrajcic Dragos, Vida Stegel, Ana Blatnik, Gasper Klancar, Mateja Krajc, Srdjan Novakovic
Summary: The study validates a new simple and direct method for detecting RNA splicing defects, reclassifying the importance of uncertain variants for patient clinical management, and providing a practical protocol for detecting splicing alterations with deep RNA sequencing.
Review
Pharmacology & Pharmacy
Dianyang Li, Wenying Yu, Maode Lai
Summary: Serine-and arginine-rich splicing factors play important roles in regulating splicing by binding to cis-acting elements in precursor mRNAs and facilitating spliceosome assembly. SR proteins also have diverse functions in RNA metabolism as they shuttle between the nucleus and cytoplasm. Overexpression and/or hyperactivation of SR proteins have been associated with tumorigenesis, suggesting their potential as therapeutic targets. This review highlights the physiological and pathological roles of SR proteins and discusses small molecules and oligonucleotides that can modulate SR protein function for future studies.
DRUG DISCOVERY TODAY
(2023)
Article
Cell Biology
Jagyeong Oh, Davide Pradella, Changwei Shao, Hairi Li, Namjeong Choi, Jiyeon Ha, Sonia Ruggiero, Xiang-Dong Fu, Xuexiu Zheng, Claudia Ghigna, Haihong Shen
Summary: Aberrant alternative splicing in breast cancer is linked to disease progression, metastasis, and patient survival. High-metastatic breast cancer cells exhibit different AS choices in genes related to cancer progression compared to low-metastatic cells. Analysis reveals novel AS features in metastatic breast tumors.
Article
Biochemistry & Molecular Biology
Elizaveta Sarygina, Anna Kozlova, Kseniia Deinichenko, Sergey Radko, Konstantin Ptitsyn, Svetlana Khmeleva, Leonid K. Kurbatov, Pavel Spirin, Vladimir S. Prassolov, Ekaterina Ilgisonis, Andrey Lisitsa, Elena Ponomarenko
Summary: The long-read RNA sequencing developed by Oxford Nanopore Technology allows for direct quantification of transcript isoforms and can be used in alternative splicing profiling. By using principal component analysis (PCA) to visualize the transcriptomic data, biospecimens can be grouped into clusters based on their gene expression. This method is useful for studying drug metabolism and transcriptome analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Jun Yao, Yu-Chen Tang, Bin Yi, Jian Yang, Yun Chai, Ni Yin, Zi-Xiang Zhang, Yi-Jun Wei, De-Chun Li, Jian Zhou
Summary: Alternative splicing plays a crucial role in the development and progression of cancer, with potential implications for patient prognosis. By analyzing RNA-Seq data from PAAD patients, differentially expressed AS events were identified, revealing associations with patient clinical characteristics and survival patterns. Additionally, splicing factors such as ESRP1 and RBM5 were found to be important in PAAD-related AS events, providing valuable insights for future therapeutic strategies.
Article
Plant Sciences
Qing Chen, Ximeng Lin, Wenlu Tang, Qian Deng, Yan Wang, Yuanxiu Lin, Wen He, Yunting Zhang, Mengyao Li, Ya Luo, Yong Zhang, Xiaorong Wang, Haoru Tang
Summary: This study systematically investigated the transcriptome complexity during strawberry fruit development, revealing thousands of new transcript isoforms and comparing the contributions of alternative transcription start or termination sites and alternative splicing to transcript complexity. The findings also shed light on isoform switches of genes during fruit maturation and their functional consequences.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Cristina Martinez-Valiente, Cristian Garcia-Ruiz, Beatriz Roson, Alessandro Liquori, Elisa Gonzalez-Romero, Raul Fernandez-Gonzalez, Isabel Gomez-Redondo, Jose Cervera, Alfonso Gutierrez-Adan, Alejandra Sanjuan-Pla
Summary: Mutations in splicing factors, such as U2AF1, in conjunction with mutations in epigenetic factors have been identified in myelodysplastic syndromes (MDS), indicating a cooperative role in MDS pathogenesis. Despite exhibiting reduced size, U2af1(mut/+) mice showed aberrant RNA splicing in hematopoietic stem/progenitor cells. Additionally, a double mutant U2af1(mut/+) Tet2(-/-) mice model displayed increased monogranulocytic precursors and functional alterations, but did not develop MDS within a 6-month observation period.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Lorenzo Agoni
Summary: Human endogenous retroviruses (HERVs) can be transcribed in various cancer types, including head and neck cancer. Despite functional defects, HERV transcripts can still be detected under specific conditions, such as cancer. The role of HERV transcription in cancer and its contribution to oncogenesis or progression are still debated.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Dong Zhang, Wenjie Zhang, Rui Sun, Zhongxian Huang
Summary: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney tumor with poor prognosis, and aberrant alternative splicing (AS) events have been identified as effective signatures for tumor prognosis prediction. A predictive model based on large-scale sequencing data was developed to decipher posttranscriptional mechanisms on tumorigenesis of ccRCC, with autophagy potentially playing a crucial role in splicing regulation.
Article
Biochemistry & Molecular Biology
Lili Xiang, Xiaofen Liu, Yanna Shi, Yajing Li, Weidong Li, Fang Li, Kunsong Chen
Summary: The research found that CmbHLH2 and CmbHLH2.1 play important roles in flower color alteration in 'Jimba' chrysanthemums, with the former playing a predominant role in the process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, General & Internal
Vincent Tano, Kagistia Hana Utami, Nur Amirah Binte Mohammad Yusof, Jocelyn Begin, Willy Wei Li Tan, Mahmoud A. Pouladi, Sarah R. Langley
Summary: In Huntington's disease, a CAG repeat expansion mutation in the HTT gene leads to dysregulation of gene splicing. Using an isogenic HD cell model, we found widespread splicing changes associated with neuronal differentiation stage and CAG length, as well as enrichment of genes related to RNA processing, neuronal function, and epigenetic modification. Our findings also suggest that splicing-associated pathogenesis may occur early in neuronal development and persist to later stages of HD.
Review
Cell Biology
Koji Kitamura, Keisuke Nimura
Summary: RNA splicing is a crucial process in the maturation of mRNA, allowing for diversity in mature mRNA through the inclusion and exclusion of introns and exons. Cancer cells develop cancer-specific mechanisms through abnormal splicing regulation to resist treatment and promote malignancy. Dysregulation of splicing is caused by factors such as mutations in splicing factors and changes in genomic sequences, impacting the splicing profile related to cancer.
Article
Genetics & Heredity
Xin Tong, Wen-Xing Li, Jihao Liang, Yang Zheng, Shao-xing Dai
Summary: This study integrated multiple transcriptome datasets to identify two distinct aging paths in blood and to identify genes and mutations associated with aging. These findings provide new insights into the aging process and age-related diseases.