Brm transactivates the telomerase reverse transcriptase (TERT) gene and modulates the splicing patterns of its transcripts in concert with p54 nrb

Taiji Ito, Hirotaka Watanabe, Nobutake Yamamichi, Shunsuke Kondo, Toshio Tando, Takeshi Haraguchi, Taketoshi Mizutani, Kouhei Sakurai, Shuji Fujita, Tomonori Izumi, Toshiaki Isobe, Hideo Iba

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27 Citations (Scopus)

Abstract

We report that a DBHS (Drosophila behaviour, human splicing) family protein, p54nrb, binds both BRG1 (Brahma-related gene 1) and Brm (Brahma), catalytic subunits of the SWI/SNF (switch/sucrose non-fermentable) chromatin remodelling complex, and also another core subunit of this complex, BAF60a. The N-terminal region of p54nrb is sufficient to pull-down other core subunits of the SWI/SNF complex, suggesting that p54nrb binds SWI/SNF-like complexes. PSF (polypyrimidine tract-binding protein-associated splicing factor), another DBHS family protein known to directly bind p54nrb, was also found to associate with the SWI/SNF-like complex. When sh (short hairpin) RNAs targeting Brm were retrovirally expressed in a BRG1-deficient human cell line (NCI-H1299), the resulting clones showed down-regulation of the TERT (telomerase reverse transcriptase) gene and an enhancement of ratios of exon-7-and-8-excluded TERT mRNA that encodes a β-site-deleted inactive protein. All of these clones display growth arrest within 2 months of the Brm-knockdown. In NCI-H1299 cells, Brm, p54nrb, PSF and RNA polymerase II phosphorylated on CTD (C-terminal domain) Ser2 specifically colocalize at a region incorporating an alternative splicing acceptor site of TERT exon 7. These findings suggest that, at the TERT gene locus in human tumour cells containing a functional SWI/SNF complex, Brm, and possibly BRG1, in concert with p54 nrb, would initiate efficient transcription and could be involved in the subsequent splicing of TERT transcripts by accelerating exon-inclusion, which partly contributes to the maintenance of active telomerase.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalBiochemical Journal
Volume411
Issue number1
DOIs
Publication statusPublished - 01-04-2008

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ito, T., Watanabe, H., Yamamichi, N., Kondo, S., Tando, T., Haraguchi, T., Mizutani, T., Sakurai, K., Fujita, S., Izumi, T., Isobe, T., & Iba, H. (2008). Brm transactivates the telomerase reverse transcriptase (TERT) gene and modulates the splicing patterns of its transcripts in concert with p54 nrb. Biochemical Journal, 411(1), 201-209. https://doi.org/10.1042/BJ20071075