TY - JOUR
T1 - Tethering KSRP, a decay-promoting AU-rich element-binding protein, to mRNAs elicits mRNA decay
AU - Chou, Chu Fang
AU - Mulky, Alok
AU - Maitra, Sushmit
AU - Lin, Wei Jye
AU - Gherzi, Roberto
AU - Kappes, John
AU - Chen, Ching Yi
PY - 2006/5
Y1 - 2006/5
N2 - 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-BPs). 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.
AB - 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-BPs). 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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U2 - 10.1128/MCB.26.10.3695-3706.2006
DO - 10.1128/MCB.26.10.3695-3706.2006
M3 - Article
C2 - 16648466
AN - SCOPUS:33646590585
VL - 26
SP - 3695
EP - 3706
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 10
ER -