TEG-1 CD2BP2 regulates stem cell proliferation and sex determination in the C. elegans germ line and physically interacts with the UAF-1 U2AF65 splicing factor

Dev Dyn. 2012 Mar;241(3):505-21. doi: 10.1002/dvdy.23735. Epub 2012 Jan 30.

Abstract

Background: For a stem cell population to exist over an extended period, a balance must be maintained between self-renewing (proliferating) and differentiating daughter cells. Within the Caenorhabditis elegans germ line, this balance is controlled by a genetic regulatory pathway, which includes the canonical Notch signaling pathway.

Results: Genetic screens identified the gene teg-1 as being involved in regulating the proliferation versus differentiation decision in the C. elegans germ line. Cloning of TEG-1 revealed that it is a homolog of mammalian CD2BP2, which has been implicated in a number of cellular processes, including in U4/U6.U5 tri-snRNP formation in the pre-mRNA splicing reaction. The position of teg-1 in the genetic pathway regulating the proliferation versus differentiation decision, its single mutant phenotype, and its enrichment in nuclei, all suggest TEG-1 also functions as a splicing factor. TEG-1, as well as its human homolog, CD2BP2, directly bind to UAF-1 U2AF65, a component of the U2 auxiliary factor.

Conclusions: TEG-1 functions as a splicing factor and acts to regulate the proliferation versus meiosis decision. The interaction of TEG-1 CD2BP2 with UAF-1 U2AF65, combined with its previously described function in U4/U6.U5 tri-snRNP, suggests that TEG-1 CD2BP2 functions in two distinct locations in the splicing cascade.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Alleles
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation / genetics
  • Cell Nucleus / metabolism
  • Cell Proliferation*
  • Female
  • Germ Cells / growth & development*
  • Germ Cells / metabolism
  • Humans
  • Male
  • Meiosis / genetics
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA Splicing Factors
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Sex Determination Processes*
  • Splicing Factor U2AF
  • Stem Cells / cytology
  • Stem Cells / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • CD2BP2 protein, human
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Nuclear Proteins
  • RNA Splicing Factors
  • Ribonucleoproteins
  • Splicing Factor U2AF
  • TEG-1 protein, C elegans
  • U2AF2 protein, human
  • UAF-1 protein, C elegans