AU-rich element–mediated mRNA decay via the butyrate response factor 1 controls cellular levels of polyadenylated replication-dependent histone mRNAs

  1. Yoon Ki Kim2
  1. From the Creative Research Initiatives Center for Molecular Biology of Translation and Division of Life Sciences, Korea University, Seoul 02841, Republic of Korea
  1. ?1 Supported in part by NRF Grants 2013R1A1A2063273 and 2016R1D1A1B03933894. To whom correspondence may be addressed. Tel.: 82-2-3290-3919; Fax: 82-2-923-9923; E-mail: ryu.incheol{at}
  2. ?2 To whom correspondence may be addressed. Tel.: 82-2-3290-3410; Fax: 82-2-923-9923; E-mail: yk-kim{at}
  1. Edited by Karin Musier-Forsyth


Replication-dependent histone (RDH) mRNAs have a nonpolyadenylated 3′-UTR that ends in a highly conserved stem-loop structure. Nonetheless, a subset of RDH mRNAs has a poly(A) tail under physiological conditions. The biological meaning of poly(A)-containing (+) RDH mRNAs and details of their biosynthesis remain elusive. Here, using HeLa cells and Western blotting, qRT-PCR, and biotinylated RNA pulldown assays, we show that poly(A)+ RDH mRNAs are post-transcriptionally regulated via adenylate- and uridylate-rich element–mediated mRNA decay (AMD). We observed that the rapid degradation of poly(A)+ RDH mRNA is driven by butyrate response factor 1 (BRF1; also known as ZFP36 ring finger protein–like 1) under normal conditions. Conversely, cellular stresses such as UV C irradiation promoted BRF1 degradation, increased the association of Hu antigen R (HuR; also known as ELAV-like RNA-binding protein 1) with the 3′-UTR of poly(A)+ RDH mRNAs, and eventually stabilized the poly(A)+ RDH mRNAs. Collectively, our results provide evidence that AMD surveils poly(A)+ RDH mRNAs via BRF1-mediated degradation under physiological conditions.


  • This work was supported by National Research Foundation of Korea (NRF) Grant NRF-2015R1A3A2033665 funded by the Korea government (Ministry of Science, ICT and Future Planning) and by a Korea University grant. The authors declare that they have no conflicts of interest with the contents of this article.

  • This article contains Fig. S1 and Table S1.

  • Received November 17, 2018.
  • Revision received April 3, 2019.

Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc.

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  1. The Journal of Biological Chemistry 294, 7558-7565.
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  3. All Versions of this Article:
    1. AC118.006766v1
    2. 294/19/7558 (most recent)

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