This study discovered that the METTL3 association with differentially expressed genes, suggested that METTL3 and the genes it regulates might serve as targets for defense against infection.
Abstract
Background: As a major regulator, methyltransferase-like 3 (METTL3) catalyzes N6-methyladenosine (m6A) modification in mRNA. The m6A modifications mediated by METTL3 influence RNA splicing, nucleocytoplasmic distribution, stability, and other functions, thereby playing a vital and indispensable role in genetic regulatory network. Although several studies have shown its critical role in mRNA fate, the global pattern of mRNA methylation alteration driven by METTL3 remain unclear. Methods: Here, a HEK293T cell line with METTL3 depletion was constructed, and RNA sequencing (RNA-seq) and methylated RNA Immunoprecipitation Sequencing (MeRIP-seq) were implemented. Additionally, quantitative Reverse Transcription PCR (qRT-PCR) technology was used to confirm some of the differentially expressed genes. Result: The mRNA methylation alteration landscape was clarified and the regions altered by m6A modification due to METTL3 deletion that was annotated and characterized, with 5763 hypomethylated/269 hypermethylated genes after METTL3 silence. Several methylation-related innate anti-infection immune genes, including MYD88, RIG-1, CYLD and IRF9, were exposed through comprehensive analysis to MeRIP-seq and RNA-seq data, and these genes were principally enriched in pathogen infection and innate immune response pathways such as Shigellosis, Yersinia infection, and the HIV-1 viral life cycle. Conclusion: Our study discovered that the METTL3 association with differentially expressed genes, suggested that METTL3 and the genes it regulates might serve as targets for defense against infection.
N6-methyladenosine (m6A) is a widespread RNA modification that regulates RNA metabolism in eukaryotes, but its distribution and function in bacteria remain poorly defined. Here, we apply GLORI sequencing to generate single-base resolution transcriptome-wide m6A maps in seven bacterial species. We identify 2,845 m6A sites during exponential growth and find extensive condition-dependent methylation dynamics in three strains. In Pseudomonas syringae, m6A remodeling is associated with virulence-related pathways. Comparative analyses reveal 455 conserved m6A site pairs enriched in genes required for growth, energy metabolism, and transmembrane transport. Integrating methylation, transcript abundance, and RNA stability analyses shows that m6A is associated with reduced mRNA abundance and increased RNA stability. We further identify the rRNA methyltransferases RlmF and RlmJ as bacterial mRNA m6A writers. Together, these findings provide a quantitative atlas of bacterial m6A and establish a foundation for understanding its regulatory and evolutionary roles.
Youyue Li, Letong Xu, Na Liu et al.· Cell Reports· 0 citations
Findings provide valuable insights into the molecular mechanisms underlying PRRSV infection and pave the way for developing more effective preventive and treatment measures.
Fiber-seq simultaneously profiles chromatin accessibility, DNA methylation, protein footprints, and genetic variation on single molecules at near—base-pair resolution, revealing how genetic and epigenetic features interact to regulate gene expression and provides a powerful new framework for dissecting immune cell function and disease mechanisms.
Emily A Madden, James T. Anderson, M. Cowles et al.· Journal of Immunology· 0 citations
A model in which mRNA modifications act combinatorially to regulate mRNA homeostasis in plants is supported, including advances in profiling technologies, single-base resolution methods, and nanopore direct RNA sequencing.
Thi Tuyet Suong Ha, S. Park, Dong-Hoon Jeong· Journal of Plant Biology· 0 citations
mRNA plays a pivotal role in cellular processes of genetic information transfer, and post-transcriptional modifications of its nucleotides enable regulation of these processes with each particular mRNA. m5C methylation is a specific RNA modification that is rather common in tRNA, rRNA, lncRNA and other types of non-coding RNAs, whereas in mRNA it is found not very often. However, the functioning of m5C-methylated mRNAs differs from the non-methylated ones quite dramatically. Of the eight m5C RNA methyltransferases in humans, only two, NSUN2 and NSUN6, were found to be capable of modifying the main portion of cellular mRNAs. A deficiency of NSUN2 and NSUN6 causes global changes in the transcriptome and translatome, and a corruption of the NSUN2 gene in humans is associated with neurodegenerative diseases and intellectual disability. Despite intensive research of m5C mRNA methylation in recent years, many aspects of this phenomenon and its significance remain problematic and far from understood. In this review, we discuss the available information on mRNA methylome biogenesis, methods for its study and analysis, effects of m5C modification on mRNA life, and place it in the general context of cell biology, attempting to draw the biological relevance of m5C mRNA methylation. We highlight the main inconsistencies and difficulties that arise, analyze their possible causes, and propose potential directions for further research that could clarify the controversial issues and provide a link between the NSUN2 deficiency and neurodegenerative diseases.
E. Babaylova, Elizaveta A. Zolotenkova, Alexey A. Malygin· Cells· 0 citations
All currently known mt-RNA modifications, their potential regulatory machinery, as well as their biological functions in tumorigenesis and metabolism are summarized.
Haixia Wang, Lili Ren, Dongling Zou et al.· MedScience· 0 citations