Roles of PSF protein and VL30 RNA in reversible gene regulation

Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12189-93. doi: 10.1073/pnas.0505179102. Epub 2005 Aug 3.

Abstract

The mammalian protein PSF contains a DNA-binding domain (DBD) that coordinately represses multiple oncogenic genes in human cell lines, indicating a role for PSF as a human tumor-suppressor protein. PSF also contains two RNA-binding domains (RBD) that form a complex with a noncoding VL30 retroelement RNA, releasing PSF from a gene and reversing repression. Thus, the DBD and RBD in PSF are linked by a mechanism of reversible gene regulation involving a noncoding RNA. This mechanism also could apply to other regulatory proteins that contain both DBD and RBD. The mouse genome has multiple copies of VL30 retroelements that are developmentally regulated, and mouse cells contain VL30 RNAs that have normal and pathological roles in gene regulation. Human chromosome 11 has a VL30 retroelement, and a VL30 EST was identified in human blastocyst cells, indicating that the PSF-VL30 RNA regulatory mechanism also could function in human cells.

Publication types

  • Comparative Study

MeSH terms

  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • DNA Primers
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Microarray Analysis
  • PTB-Associated Splicing Factor
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA, Untranslated / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Retroelements / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • DNA-Binding Proteins
  • PTB-Associated Splicing Factor
  • RNA, Untranslated
  • RNA-Binding Proteins
  • Retroelements