Lee Spraggon

Memorial Sloan-Kettering Cancer Center, New York City, New York, United States

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Publications (3)10.82 Total impact

  • Lee Spraggon, Luca Cartegni
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    ABSTRACT: Next-generation antisense technologies are re-emerging as viable and powerful approaches to the treatment of several genetic diseases. Similar strategies are also being applied to cancer therapy. Reprogramming of the expression of endogenous oncogenic products to replace them with functional antagonists, by interfering with alternative splicing (AS) or polyadenylation, provides a promising novel approach to address acquired drug resistance and previously undruggable targets.
    Drug Discovery Today Therapeutic Strategies 09/2013;
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    Lee Spraggon, Luca Cartegni
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    ABSTRACT: Pre-mRNA splicing and polyadenylation are critical steps in the maturation of eukaryotic mRNA. U1 snRNP is an essential component of the splicing machinery and participates in splice-site selection and spliceosome assembly by base-pairing to the 5' splice site. U1 snRNP also plays an additional, nonsplicing global function in 3' end mRNA processing; it actively suppresses the polyadenylation machinery from using early, mostly intronic polyadenylation signals which would lead to aberrant, truncated mRNAs. Thus, U1 snRNP safeguards pre-mRNA transcripts against premature polyadenylation and contributes to the regulation of alternative polyadenylation. Here, we review the role of U1 snRNP in 3' end mRNA processing, outline the evidence that led to the recognition of its physiological, general role in inhibiting polyadenylation, and finally highlight the possibility of manipulating this U1 snRNP function for therapeutic purposes in cancer.
    International Journal of Cell Biology 01/2013; 2013:846510.
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    ABSTRACT: The microRNA (miRNA)-induced silencing complex (miRISC) controls gene expression by a posttranscriptional mechanism involving translational repression and/or promoting messenger RNA (mRNA) deadenylation and degradation. The GW182/TNRC6 (GW) family proteins are core components of the miRISC and are essential for miRNA function. We show that mammalian GW proteins have distinctive functions in the miRNA pathway, with GW220/TNGW1 being essential for the formation of GW/P bodies containing the miRISC. miRISC aggregation and formation of GW/P bodies sequestered and stabilized translationally repressed target mRNA. Depletion of GW220 led to the loss of GW/P bodies and destabilization of miRNA-targeted mRNA. These findings support a model in which the cellular localization of the miRISC regulates the fate of the target mRNA.
    The Journal of Cell Biology 08/2012; 198(4):529-44. · 10.82 Impact Factor