Ribosomal protein L11 associates with c-Myc at 5 S rRNA and tRNA genes and regulates their expression.
The c-Myc oncoprotein promotes cell growth by enhancing ribosomal biogenesis. Overexpression of c-Myc and aberrant ribosomal biogenesis lead to deregulated cell growth and tumorigenesis. Hence, c-Myc activity and ribosomal biogenesis must be tightly coordinated during normal homeostasis. We previously found that ribosomal protein L11 inhibits c-Myc activity by blocking the recruitment of its co-activator transformation/transcription domain-associated protein (TRRAP) to the promoter regions of c-Myc target genes that are transcribed by RNA polymerases I and II. In this study, we extended the role of L11 to the regulation of c-Myc-driven transcription of the 5 S rRNA and tRNA genes by RNA polymerase III. L11 co-resided with c-Myc at the 5 S rRNA and tRNA genes and significantly inhibited the binding of TRRAP to these genes. Knocking down endogenous L11 enhanced c-Myc-dependent transcription of these genes. Interestingly, in response to ribosomal stress induced by the treatment of cells with a low dose of actinomycin D or serum starvation, L11 binding to these genes was increased, and inversely TRRAP binding to these genes was decreased. Consistently, knockdown of L11 rescued the reduction of the expression of these genes by the two treatments. These results demonstrate that L11 suppresses c-Myc-dependent and RNA polymerase III-catalyzed transcription of 5 S rRNA and tRNA genes in response to ribosomal stress, ensuring a tight coordination between c-Myc activity and ribosomal biogenesis.
Dai
Mu-Shui
MS
Department of Molecular and Medical Genetics, School of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA. daim@ohsu.edu
Sun
Xiao-Xin
XX
Lu
Hua
H
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism; D012341:RNA, Ribosomal, 5S / Q000096:biosynthesis* / Q000235:genetics; D012343:RNA, Transfer / Q000096:biosynthesis* / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C489427:MYC protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D012341:RNA, Ribosomal, 5S; D012269:Ribosomal Proteins; C027624:ribosomal protein L11; C113829:transformation-transcription domain-associated protein; D012343:RNA, Transfer; D012320:RNA Polymerase III