Inhibiting the RNA methyltransferase METTL3 or its interaction with EIF3H to suppress oncogene translation and tumorigenesis

Abstract

Provided herein are method of treating cancer using agents that inhibit the interaction between Methyltransferase like 3 (METTL3) and Eukaryotic Translation Initiation Factor 3 Subunit H (EIF3h), and optionally agents that inhibit Bromodomain-containing protein 4 (BRD4). The present disclosure demonstrates the topology of individual polyribosomes with single METTL3 foci found in close proximity to 5′ cap-binding proteins, revealing a previously unknown direct physical and functional interaction between METTL3 and the eukaryotic translation initiation factor 3 subunit h (eIF3h).

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