Involvement of microRNA in AU-rich element-mediated mRNA instability

Cell. 2005 Mar 11;120(5):623-34. doi: 10.1016/j.cell.2004.12.038.

Qing Jing ¹, Shuang Huang, Sabine Guth, Tyler Zarubin, Andrea Motoyama, Jianming Chen, Franco Di Padova, Sheng-Cai Lin, Hermann Gram, Jiahuai Han

Affiliations

Affiliation

1 Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

PMID: 15766526 DOI: 10.1016/j.cell.2004.12.038

Abstract

AU-rich elements (AREs) in the 3' untranslated region (UTR) of unstable mRNAs dictate their degradation. An RNAi-based screen performed in Drosophila S2 cells has revealed that Dicer1, Argonaute1 (Ago1) and Ago2, components involved in MicroRNA (miRNA) processing and function, are required for the rapid decay of mRNA containing AREs of tumor necrosis factor-alpha. The requirement for Dicer in the instability of ARE-containing mRNA (ARE-RNA) was confirmed in HeLa cells. We further observed that miR16, a human miRNA containing an UAAAUAUU sequence that is complementary to the ARE sequence, is required for ARE-RNA turnover. The role of miR16 in ARE-RNA decay is sequence-specific and requires the ARE binding protein tristetraprolin (TTP). TTP does not directly bind to miR16 but interacts through association with Ago/eiF2C family members to complex with miR16 and assists in the targeting of ARE. miRNA targeting of ARE, therefore, appears to be an essential step in ARE-mediated mRNA degradation.

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