title: Ribosomal proteins L5 and L11 co-operatively inactivate c-Myc via RNA-induced silencing complex.
abstract: Oncogene MYC is highly expressed in many human cancers and functions as a global regulator of ribosome biogenesis. Previously, we reported that ribosomal protein (RP) L11 binds to c-Myc and inhibits its transcriptional activity in response to ribosomal stress. Here, we show that RPL5, co-operatively with RPL11, guides the RNA-induced silencing complex (RISC) to c-Myc mRNA and mediates the degradation of the mRNA, consequently leading to inhibition of c-Myc activity. Knocking down of RPL5 induced c-Myc expression at both mRNA and protein levels, whereas overexpression of RPL5 suppressed c-Myc expression and activity. Immunoprecipitation revealed that RPL5 binds to 3'UTR of c-Myc mRNA and two subunits of RISC, TRBP (HIV-1 TAR RNA-binding protein) and Ago2, mediating the targeting of c-Myc mRNA by miRNAs. Interestingly, RPL5 and RPL11 co-resided on c-Myc mRNA and suppressed c-Myc expression co-operatively. These findings uncover a mechanism by which these two RPs can co-operatively suppress c-Myc expression, allowing a tightly controlled ribosome biogenesis in cells.
authors.affiliation: Department of Biochemistry and Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: J-M
authors.initials: JM
authors.lastname: Liao
authors.affiliation: Department of Biochemistry and Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Lady Davis Institute for Medical Research, McGill University AIDS Centre, Montréal, Québec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Gatignol
authors.affiliation: Department of Biochemistry and Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Lu
mesh_terms: D020413:3' Untranslated Regions; D060565:Argonaute Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003470:Culture Media / Q000494:pharmacology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism; D000099253:Trans-Activation Responsive RNA-Binding Protein
chemical_list: D020413:3' Untranslated Regions; D060565:Argonaute Proteins; D003470:Culture Media; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D000099253:Trans-Activation Responsive RNA-Binding Protein; C466422:AGO2 protein, human; C489427:MYC protein, human; C027624:ribosomal protein L11; C549166:ribosomal protein L5, human