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).

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: The 3?-5? exonuclease, Dis3l2, is responsible for the decay of uridylated pre-let-7 miRNA. Biochemical reconstitution assays revealed that 3? oligouridylation stimulates Dis3l2 activity in vitro, and knockdown of Dis3l2 in mouse embryonic stem cells leads to the stabilization of pre-let-7 miRNA. These Dis3l2-depleted stem cells displayed elevated expression of pluripotency genes and delayed differentiation. The present disclosure establishes 3? oligouridylation as an RNA decay signal for Dis3l2 and identifies the first physiological RNA substrate of this exonuclease.

Abstract: Provided herein are compositions and methods related to modulation of progenitor microRNAs (pro-miRNAs), such as for the treatment of cancer.

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogenesis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: The 3?-5? exonuclease, Dis3l2, is responsible for the decay of uridylated pre-let-7 miRNA. Biochemical reconstitution assays revealed that 3? oligouridylation stimulates Dis3l2 activity in vitro, and knockdown of Dis3l2 in mouse embryonic stem cells leads to the stabilization of pre-let-7 miRNA. These Dis3l2-depleted stem cells displayed elevated expression of pluripotency genes and delayed differentiation. The present disclosure establishes 3? oligouridylation as an RNA decay signal for Dis3l2 and identifies the first physiological RNA substrate of this exonuclease.

Abstract: The present embodiments provide for compositions and methods that regulate microRNA-binding protein-mediated miRNA biogensis; for example Lin28-mediated biogenesis of let-7; and in particular Lin28A-recruited 3? terminal uridylyl transferase (TUTase) uridylation of pre-let-7. A particular embodiment provide compositions and methods for screening for agents that inhibit TUTase-dependent Lin28A-mediated repression of let-7 miRNA.

Abstract: The present invention relates generally to methods to regulate microRNA (miRNA) biogenesis, in particular the regulation of the processing of pri-miRNA to mature miRNA by Lin-28 and/or variants such as Lin28B. In particular, the present invention relates to methods and compositions comprising at least one agent which inhibits Lin-28 function or activity and/or expression to increase the processing of pri-mRNA to mature miRNA. More specifically, one aspect of the invention is directed to treating and/or preventing cancer in a subject by administering an agent that inhibits Lin-28 activity or expression to a subject, preferably a human subject.

Abstract: The present invention relates generally to methods to regulate microRNA (miRNA) biogenesis, in particular the regulation of the processing of pri-miRNA to mature miRNA by Lin-28 and/or variants such as Lin28B. In particular, the present invention relates to methods and compositions comprising at least one agent which inhibits Lin-28 function or activity and/or expression to increase the processing of pri-mRNA to mature miRNA. More specifically, one aspect of the invention is directed to treating and/or preventing cancer in a subject by administering an agent that inhibits Lin-28 activity or expression to a subject, preferably a human subject.