title: HuR uses AUF1 as a cofactor to promote p16INK4 mRNA decay.
abstract: In this study, we show that HuR destabilizes p16(INK4) mRNA. Although the knockdown of HuR or AUF1 increased p16 expression, concomitant AUF1 and HuR knockdown had a much weaker effect. The knockdown of Ago2, a component of the RNA-induced silencing complex (RISC), stabilized p16 mRNA. The knockdown of HuR diminished the association of the p16 3' untranslated region (3'UTR) with AUF1 and vice versa. While the knockdown of HuR or AUF1 reduced the association of Ago2 with the p16 3'UTR, Ago2 knockdown had no influence on HuR or AUF1 binding to the p16 3'UTR. The use of EGFP-p16 chimeric reporter transcripts revealed that p16 mRNA decay depended on a stem-loop structure present in the p16 3'UTR, as HuR and AUF1 destabilized EGFP-derived chimeric transcripts bearing wild-type sequences but not transcripts with mutations in the stem-loop structure. In senescent and HuR-silenced IDH4 human diploid fibroblasts, the EGFP-p16 3'UTR transcript was more stable. Our results suggest that HuR destabilizes p16 mRNA by recruiting the RISC, an effect that depends on the secondary structure of the p16 3'UTR and requires AUF1 as a cofactor.
authors.affiliation: Research Center on Aging, Department of Biochemistry and Molecular Biology, Peking University Health Science Center, Beijing, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Chang
authors.forename: Jie
authors.initials: J
authors.lastname: Yi
authors.forename: Gaier
authors.initials: G
authors.lastname: Guo
authors.forename: Xinwen
authors.initials: X
authors.lastname: Liu
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
authors.forename: Tanjun
authors.initials: T
authors.lastname: Tong
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Cui
authors.forename: Ming
authors.initials: M
authors.lastname: Zhan
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.forename: Wengong
authors.initials: W
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D034743:RNA-Induced Silencing Complex / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034743:RNA-Induced Silencing Complex