Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover |
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Authors: | Yamashita Akio Chang Tsung-Cheng Yamashita Yukiko Zhu Wenmiao Zhong Zhenping Chen Chyi-Ying A Shyu Ann-Bin |
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Institution: | Department of Biochemistry and Molecular Biology, The University of Texas Medical School, Houston, Texas 77030, USA. |
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Abstract: | In mammalian cells, the enzymatic pathways involved in cytoplasmic mRNA decay are incompletely defined. In this study, we have used two approaches to disrupt activities of deadenylating and/or decapping enzymes to monitor effects on mRNA decay kinetics and trap decay intermediates. Our results show that deadenylation is the key first step that triggers decay of both wild-type stable and nonsense codon-containing unstable beta-globin mRNAs in mouse NIH3T3 fibroblasts. PAN2 and CCR4 are the major poly(A) nucleases active in cytoplasmic deadenylation that have biphasic kinetics, with PAN2 initiating deadenylation followed by CCR4-mediated poly(A) shortening. DCP2-mediated decapping takes place after deadenylation and may serve as a backup mechanism for triggering mRNA decay when initial deadenylation by PAN2 is compromised. Our findings reveal a functional link between deadenylation and decapping and help to define in vivo pathways for mammalian cytoplasmic mRNA decay. |
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