期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 26, 期 10, 页码 3695-3706出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.26.10.3695-3706.2006
关键词
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资金
- NIAID NIH HHS [R01 AI047714, AI47714] Funding Source: Medline
- NIGMS NIH HHS [GM68758, R01 GM068758] Funding Source: Medline
Inherently unstable mRNAs contain AU-rich elements (AREs) in their 3' untranslated regions that act as mRNA stability determinants by interacting with ARE-binding proteins (ARE-BlPs). We have destabilized two mRNAs by fusing sequence-specific RNA-binding proteins to KSRP, a decay-promoting ARE-BP, in a tethering assay. These results support a model that KSRP recruits mRNA decay machinery/factors to elicit decay. The ability of tethered KSRP to elicit mRNA decay depends on functions of known mRNA decay enzymes. By targeting the Rev response element of human immunodeficiency virus type 1 by using Rev-KSRP fusion protein, we degraded viral mRNA, resulting in a dramatic reduction of viral replication. These results provide a foundation for the development of novel therapeutic strategies to inhibit specific gene expression in patients with acquired or hereditary diseases.
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