Concerted action of poly(A) nucleases and decapping enzyme in mammalian mRNA turnover

Akio Yamashita, Tsung Cheng Chang, Yukiko Yamashita, Wenmiao Zhu, Zhenping Zhong, Chyi Ying A Chen, Ann Bin Shyu

Research output: Contribution to journalArticlepeer-review

338 Scopus citations


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 β-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.

Original languageEnglish (US)
Pages (from-to)1054-1063
Number of pages10
JournalNature Structural and Molecular Biology
Issue number12
StatePublished - Dec 27 2005

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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