snoRNAs are a novel class of biologically relevant Myc targets

BMC Biol. 2015 Apr 16:13:25. doi: 10.1186/s12915-015-0132-6.

Abstract

Background: Myc proteins are essential regulators of animal growth during normal development, and their deregulation is one of the main driving factors of human malignancies. They function as transcription factors that (in vertebrates) control many growth- and proliferation-associated genes, and in some contexts contribute to global gene regulation.

Results: We combine chromatin immunoprecipitation-sequencing (ChIPseq) and RNAseq approaches in Drosophila tissue culture cells to identify a core set of less than 500 Myc target genes, whose salient function resides in the control of ribosome biogenesis. Among these genes we find the non-coding snoRNA genes as a large novel class of Myc targets. All assayed snoRNAs are affected by Myc, and many of them are subject to direct transcriptional activation by Myc, both in Drosophila and in vertebrates. The loss of snoRNAs impairs growth during normal development, whereas their overexpression increases tumor mass in a model for neuronal tumors.

Conclusions: This work shows that Myc acts as a master regulator of snoRNP biogenesis. In addition, in combination with recent observations of snoRNA involvement in human cancer, it raises the possibility that Myc's transforming effects are partially mediated by this class of non-coding transcripts.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Cell Line, Tumor
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Gene Expression Regulation, Developmental
  • Genes, Insect
  • Humans
  • Models, Biological
  • Promoter Regions, Genetic / genetics
  • Protein Binding / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Small Nucleolar / genetics
  • RNA, Small Nucleolar / metabolism*
  • Ribosomal Proteins / genetics
  • Ribosomal Proteins / metabolism
  • Ribosomes / metabolism
  • Vertebrates / genetics

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA, Small Nucleolar
  • Ribosomal Proteins