This review discusses the available information on mRNA methylome biogenesis, methods for its study and analysis, effects of m5C modification on mRNA life, and places it in the general context of cell biology, attempting to draw the biological relevance of m5C mRNA methylation.
Abstract
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.
The molecular mechanisms by which m6A regulates both coding and noncoding RNAs in HCC are summarized, the functional roles of key m6A regulators in hepatocarcinogenesis are highlighted, and the therapeutic potential of targeting the m6A machinery in HCC is discussed.
Xinning Luo, Cuiying Qin, Yi Feng et al.· Discover Oncology· 0 citations
N6-methyladenosine profiles of mRNA transcripts regulate their translocation from the nucleus to the cytosol, stability, and translational efficiency; hence, they have been implicated in gene expression and disease progression. The m6A-methylation is widely associated with various cancers and neurological, cardiovascular, and developmental disorders, which demand early diagnosis. A robust m6A-motif prediction is necessary to enable us to identify the regulatory nucleic acid sequences that determine mRNA fate in normal and diseased conditions. We have developed a transcript-aware computational pipeline, termed m6AFunctional Index in Transcription (m6A-FINDiT), that can identify potential m6A sites on mRNA transcripts, considering molecular intricacies associated with their secondary structure. This tool can separately identify m6A motifs within the coding sequences as well as in non-translatable regions, i.e., 5’UTR and 3’UTR, of mRNA transcripts. Parallelly, another technique was developed that quantifies specific m6A methylation motifs through a probe-based ELISA process, MAQ-G. This second method successfully validated the N⁶-methyladenosine motifs predicted by the initially developed motif-finder program. This integrated m6A-FINDiT and MAQ-G, coupled with a real-time qPCR assay, could correlate the methylation profiles of N6-methyladenosine motifs with the expression and stability contours of a gene. To establish the physiological implications of these techniques, we chose three tumour-suppressor genes, viz., IRF8, RB1, and TP53 mRNA transcripts, which may undergo m6A methylation at certain DRACH motifs. The m6A-FINDiT pipeline could successfully predict the specific m6A motifs, and the MAQ-G confirmed the methylation profile of the latter. These duo techniques hold potential for use in clinical settings for early cancer detection.
Neha Choudhari, H. Srinivas, Praneeth Sai Tadepalli et al.· Molecular Biology Reports· 0 citations
This review focuses on the interplay between immunity and epitranscriptomics and explores the direct and indirect effects of m6A modification on T cells and highlights the pivotal role of m6A regulation in T cell biology and its potential to optimize next-generation immunotherapies.
Yumna A. Butt, Nordin D. Zandhuis, I. Foskolou· Immuno· 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
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
N6-methyladenosine (m6A) is a prevalent epitranscriptional modification in RNA that is crucial for RNA metabolism and biogenesis. Accumulating evidence reveals a complex interplay between m6A and protein post-translational modifications (PTMs)-covalent additions of chemical groups or structural alterations to nascent proteins during or after biosynthesis. This crosstalk involves in disease development and drug response by altering protein properties and functions. Nevertheless, comprehensive discussion about the roles and mechanisms of m6A and PTMs crosstalk is limited. Here, we present an up-to-date review of this emerging and complex interplay in disease and therapeutic response. We first summarize the crosstalk between m6A and PTMs such as ubiquitination, lactylation, acetylation, phosphorylation, and methylation, organizing our discussion around the three major regulatory factors m6A writers, erasers, and readers. Next, we explore the mechanism of m6A-PTMs crosstalk involved in the pathogenesis and development of diseases, including various cancers, metabolic disorders, and inflammatory diseases. Moreover, we discuss the role of m6A-PTMs crosstalk in drug response, focusing on chemotherapy drugs. In summary, this review provides a framework for understanding the regulatory networks of m6A-PTMs crosstalk in disease pathogenesis, development, and therapeutic response, highlighting potential treatment strategies based on this interplay and suggesting future research directions.
Xinyi Li, Li-Ting Yang, Xian-Min Zhou et al.· Biochimica et Biophysica Act...· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
