Aberrant expression of methyltransferases and demethylases may augment tumor initiation, proliferation and metastasis through RNA modification, such as mA and mC. However, activity of pseudouridine (Ψ) modification of RNA remains unknown in glioma, the most common malignant intracranial tumor. In this study, we explored the expression profiles of the Ψ synthase genes in glioma and constructed an efficient prediction model for glioma prognosis based on the CGGA and TCGA datasets. In addition, the risk-score signature was positively associated with malignancy of gliomas and the abundance of tumor-infiltrating immune cells such as macrophages M0 and regulatory T cells (Tregs), but negatively associated with the abundance of monocytes, NK cell activation and T cell CD4 naive. In terms of mechanism, the risk-score signature was positively associated with the expression of inflammatory molecules such as S100A11 and CASP4 in glioma. Overall, this study provided evidence for the activity of RNA Ψ modification in glioma malignancy and local immunity.
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http://dx.doi.org/10.3389/fcell.2021.727595 | DOI Listing |
Mol Ther Nucleic Acids
December 2024
Centre for Human Technologies (CHT), RNA System Biology Lab, Istituto Italiano di Tecnologia (IIT), Via Enrico Melen, 83, 16152 Genova, Italy.
RNA modifications play a crucial role in regulating gene expression by altering RNA structure and modulating interactions with RNA-binding proteins (RBPs). In this study, we explore the impact of specific RNA chemical modifications-N-methyladenosine (m⁶A), A-to-I editing, and pseudouridine (Ψ)-on RNA secondary structure and protein-RNA interactions. Utilizing genome-wide data, including RNA secondary structure predictions and protein-RNA interaction datasets, we classify proteins into distinct categories based on their binding behaviors: modification specific and structure independent, or modification unspecific and structure dependent.
View Article and Find Full Text PDFACS Bio Med Chem Au
December 2024
Department of Bioengineering, Indian Institute of Science, Bengaluru 560012, India.
Base modification and the use of lipid nanoparticles are thought to be essential for efficient in vivo delivery and expression of mRNA. However, for ex vivo immune cell engineering, the need for either of the two is unclear. Previous reports have suggested that nucleic acids may be efficiently delivered to immune cells ex vivo, through a nonendosomal delivery route, but the need for base modification has not been determined.
View Article and Find Full Text PDFNeurodegenerative disorders encompass a group of age-related conditions characterized by the gradual decline in both the structure and functionality of the central nervous system (CNS). RNA modifications, arising from the epitranscriptome or RNA-modifying protein mutations, have recently been observed to contribute significantly to neurodegenerative disorders. Specific modifications like N6-methyladenine (m6A), N1-methyladenine (m1A), 5-methylcytosine (m5C), pseudouridine and adenosine-to-inosine (A-to-I) play key roles, with their regulators serving as crucial therapeutic targets.
View Article and Find Full Text PDFMol Cell
December 2024
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Dr. Aiguader 88, Barcelona 08003, Spain; Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain; ICREA, Passeig Lluís Companys 23, Barcelona 08010, Spain. Electronic address:
Mammalian ribosomal RNA (rRNA) molecules are highly abundant RNAs, decorated with over 220 rRNA modifications. Previous works have shown that some rRNA modification types can be dynamically regulated; however, how and when the mammalian rRNA modification landscape is remodeled remains largely unexplored. Here, we employ direct RNA sequencing to chart the human and mouse rRNA epitranscriptome across tissues, developmental stages, cell types, and disease.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopaedic Department of Tongji Hospital, Tongji University, 389 Xincun Road, Shanghai 200065, China.
Utilizing base-conversion (BC) techniques, single-base resolution profiling of RNA and DNA modifications has significantly advanced. BC strategies range from one-way conversions (e.g.
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