title: Combinatorial mRNA binding by AUF1 and Argonaute 2 controls decay of selected target mRNAs.
abstract: The RNA-binding protein AUF1 binds AU-rich elements in 3'-untranslated regions to regulate mRNA degradation and/or translation. Many of these mRNAs are predicted microRNA targets as well. An emerging theme in post-transcriptional control of gene expression is that RNA-binding proteins and microRNAs co-regulate mRNAs. Recent experiments and bioinformatic analyses suggest this type of co-regulation may be widespread across the transcriptome. Here, we identified mRNA targets of AUF1 from a complex pool of cellular mRNAs and examined a subset of these mRNAs to explore the links between RNA binding and mRNA degradation for both AUF1 and Argonaute 2 (AGO2), which is an essential effector of microRNA-induced gene silencing. Depending on the specific mRNA examined, AUF1 and AGO2 binding is proportional/cooperative, reciprocal/competitive or independent. For most mRNAs in which AUF1 affects their decay rates, mRNA degradation requires AGO2. Thus, AUF1 and AGO2 present mRNA-specific allosteric binding relationships for co-regulation of mRNA degradation.
authors.affiliation: Department of Biochemistry and Molecular Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.
authors.forename: Xiangyue
authors.initials: X
authors.lastname: Wu
authors.forename: Sandra
authors.initials: S
authors.lastname: Chesoni
authors.forename: Gaelle
authors.initials: G
authors.lastname: Rondeau
authors.forename: Christi
authors.initials: C
authors.lastname: Tempesta
authors.forename: Reshma
authors.initials: R
authors.lastname: Patel
authors.forename: Sandy
authors.initials: S
authors.lastname: Charles
authors.forename: Naznin
authors.initials: N
authors.lastname: Daginawala
authors.forename: Beth E
authors.initials: BE
authors.lastname: Zucconi
authors.forename: Aparna
authors.initials: A
authors.lastname: Kishor
authors.forename: Guangwu
authors.initials: G
authors.lastname: Xu
authors.forename: Yufang
authors.initials: Y
authors.lastname: Shi
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Li
authors.forename: Patricia
authors.initials: P
authors.lastname: Irizarry-Barreto
authors.forename: John
authors.initials: J
authors.lastname: Welsh
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Wilson
authors.forename: Gary
authors.initials: G
authors.lastname: Brewer
mesh_terms: D020413:3' Untranslated Regions; D060565:Argonaute Proteins / Q000378:metabolism*; D006367:HeLa Cells; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; C466422:AGO2 protein, human; D060565:Argonaute Proteins; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D012333:RNA, Messenger