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  • The multifaceted effects of...
    Widagdo, Jocelyn; Anggono, Victor; Wong, Justin J.-L.

    Trends in genetics, April 2022, 2022-04-00, 20220401, Letnik: 38, Številka: 4
    Journal Article

    N6-methyladenosine or m6A modification to mRNAs is now recognised as a key regulator of gene expression and protein translation. The fate of m6A-modified mRNAs is decoded by m6A readers, mostly found in the cytoplasm, except for the nuclear-localised YTHDC1. While earlier studies have implicated YTHDC1–m6A functions in alternative splicing and mRNA export, recent literature has expanded its close association to the chromatin-associated, noncoding and regulatory RNAs to fine-tune transcription and gene expression in cells. Here, we summarise current progress in the study of YTHDC1 function in cells, highlighting its multiple modes of action in regulating gene expression, and propose the formation of YTHDC1 nuclear condensates as a general mechanism that underlies its diverse functions in the nucleus. YTHDC1 interacts with m6A-modified RNAs to regulate multiple steps of RNA metabolism in the nucleus.YTHDC1 is widely associated with transcriptional activation (via enhancer RNA-mediated crossregulation with active epigenetic marks).YTHDC1 transcriptional repressive action is largely associated with transposable elements and long ncRNAs.The diversity in YTHDC1–m6A functions is linked to their ability to promote membraneless nuclear subcompartments, such as the nuclear speckles.