Fecha de publicación:
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Fuente:
PubMed "industrial biotechnology"
Biochim Biophys Acta Gene Regul Mech. 2026 Oct 20:195188. doi: 10.1016/j.bbagrm.2026.195188. Online ahead of print.ABSTRACTTranscription serves as the primary mRNA blueprint for gene expression; however, transcription function is further regulated by co-transcriptional and post-transcriptional mechanisms, including N6-methyladenosine (m6A), the most widespread internal mRNA modification. The mammalian m6A landscape is primarily established by the METTL3-METTL14 writer complex, with METTL3 serving as its catalytic subunit, while accessory writer components, erasers, and readers contribute to the regulation and interpretation of m6A marks. Conventional bulk sequencing averages m6A profiles across large cell populations, masking cell- and tissue-specific heterogeneity in m6A deposition and interpretation. Studies show that the functional outcome of METTL3-mediated m6A deposition depends on the co-expression of the reader and eraser proteins in the same cell, and that these vary across cell types, developmental stages, and tissue compartments. Recent single-cell and spatial epitranscriptomic technologies are beginning to resolve this context-dependent regulation, revealing that m6A can promote mRNA decay, translation, stabilization, or altered splicing depending on cellular context. In this review, we discuss emerging technologies for single-cell and spatially resolved m6A profiling, using METTL3 as a conceptual framework for understanding how m6A deposition is linked to transcriptional state and subsequently decoded by cell-specific regulatory machinery. We further discuss their applications, technological challenges, multi-omics integration, and clinical potential in development, immunity, neuronal biology, and cancer.PMID:42901376 | DOI:10.1016/j.bbagrm.2026.195188