The long and the short of TRF2 in neurogenesis

Ioannis Grammatikakis, Peisu Zhang, Mark P. Mattson, Myriam Gorospe

Research output: Contribution to journalArticle

Abstract

Gene expression patterns change dramatically during neuronal development. Proliferating cells, including neural stem cells (NSCs), express telomere repeat-binding factor 2 (TRF2), a nuclear protein that associates with telomeric proteins, DNA, and RNA telomeres. In NSCs TRF2 also binds to the transcription regulator REST to facilitate repression of numerous neuron-specific genes, thereby keeping the NSCs in a self-renewing state. Upon neuronal differentiation, TRF2 levels decline, REST-regulated neuronal genes are derepressed, and a short isoform of TRF2 arises (TRF2-S) which localizes in the cytoplasm, associates with different subsets of proteins and transcripts, and mobilizes axonal G-rich mRNAs. We recently identified two RNA-binding proteins, HNRNPH1 and H2 (referred to jointly as HNRNPH due to their high homology), which mediate the alternative splicing of an exon required for the expression of full-length TRF2. As HNRNPH levels decline during neurogenesis, TRF2 abundance decreases and TRF2-S accumulates. Here, we discuss the shared and unique functions of TRF2 and TRF2-S, the distinct subcellular compartment in which each isoform resides, the subsets of proteins and nucleic acids with which each interacts, and the functional consequences of these ribonucleoprotein interactions. This paradigm illustrates the dynamic mechanisms through which splicing regulation by factors like HNRNPH enable distinct protein functions as cells adapt to developmental programs such as neurogenesis.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalCell Cycle
DOIs
StateAccepted/In press - Oct 14 2016
Externally publishedYes

Fingerprint

Telomere-Binding Proteins
Neurogenesis
Neural Stem Cells
Protein Isoforms
Proteins
Ribonucleoproteins
RNA-Binding Proteins
Telomere
Alternative Splicing
Nuclear Proteins
Nucleic Acids
Genes
Exons
Cytoplasm

Keywords

  • HNRNPH
  • Neuronal development
  • REST
  • ribonucleoprotein complex
  • RNA-binding proteins
  • splicing

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Grammatikakis, I., Zhang, P., Mattson, M. P., & Gorospe, M. (Accepted/In press). The long and the short of TRF2 in neurogenesis. Cell Cycle, 1-7. https://doi.org/10.1080/15384101.2016.1222339

The long and the short of TRF2 in neurogenesis. / Grammatikakis, Ioannis; Zhang, Peisu; Mattson, Mark P.; Gorospe, Myriam.

In: Cell Cycle, 14.10.2016, p. 1-7.

Research output: Contribution to journalArticle

Grammatikakis, I, Zhang, P, Mattson, MP & Gorospe, M 2016, 'The long and the short of TRF2 in neurogenesis', Cell Cycle, pp. 1-7. https://doi.org/10.1080/15384101.2016.1222339
Grammatikakis I, Zhang P, Mattson MP, Gorospe M. The long and the short of TRF2 in neurogenesis. Cell Cycle. 2016 Oct 14;1-7. https://doi.org/10.1080/15384101.2016.1222339
Grammatikakis, Ioannis ; Zhang, Peisu ; Mattson, Mark P. ; Gorospe, Myriam. / The long and the short of TRF2 in neurogenesis. In: Cell Cycle. 2016 ; pp. 1-7.
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