PARN deadenylase is involved in miRNA-dependent degradation of TP53 mRNA in mammalian cells.

Abstract:

:mRNA deadenylation is under the control of cis-acting regulatory elements, which include AU-rich elements (AREs) and microRNA (miRNA) targeting sites, within the 3' untranslated region (3' UTRs) of eukaryotic mRNAs. Deadenylases promote miRNA-induced mRNA decay through their interaction with miRNA-induced silencing complex (miRISC). However, the role of poly(A) specific ribonuclease (PARN) deadenylase in miRNA-dependent mRNA degradation has not been elucidated. Here, we present evidence that not only ARE- but also miRNA-mediated pathways are involved in PARN-mediated regulation of the steady state levels of TP53 mRNA, which encodes the tumor suppressor p53. Supporting this, Argonaute-2 (Ago-2), the core component of miRISC, can coexist in complexes with PARN resulting in the activation of its deadenylase activity. PARN regulates TP53 mRNA stability through not only an ARE but also an adjacent miR-504/miR-125b-targeting site in the 3' UTR. More importantly, we found that miR-125b-loaded miRISC contributes to the specific recruitment of PARN to TP53 mRNA, and that can be reverted by the ARE-binding protein HuR. Together, our studies provide new insights into the role of PARN in miRNA-dependent control of mRNA decay and into the mechanisms behind the regulation of p53 expression.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Zhang X,Devany E,Murphy MR,Glazman G,Persaud M,Kleiman FE

doi

10.1093/nar/gkv959

subject

Has Abstract

pub_date

2015-12-15 00:00:00

pages

10925-38

issue

22

eissn

0305-1048

issn

1362-4962

pii

gkv959

journal_volume

43

pub_type

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