The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice

Bradley A. Carlson, Ulrich Schweizer, Christine Perella, Rajeev Kumar Shrimali, Lionel Feigenbaum, Liya Shen, Svetlana Speransky, Thomas Floss, Soon Jeong Jeong, Jennifer Watts, Victoria Hoffmann, Gerald F. Combs, Vadim N. Gladyshev, Dolph L. Hatfield

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

STAF [Sec (selenocysteine) tRNA gene transcription activating factor] is a transcription activating factor for a number of RNA Pol III- and RNA Pol II-dependent genes including the Trsp [Sec tRNA gene], which in turn controls the expression of all selenoproteins. Here, the role of STAF in regulating expression of Sec tRNA and selenoproteins was examined.We generated transgenic mice expressing the Trsp transgene lacking the STAF-binding site andmade these mice dependent on the transgene for survival by removing the wild-type Trsp. The level of Sec tRNA was unaffected or slightly elevated in heart and testis, but reduced ∼60%in liver and kidney, ∼70% in lung and spleen and ∼80% in brain and muscle compared with the corresponding organs in control mice. Moreover, the ratio of the two isoforms of Sec tRNA that differ by methylation at position 34 (Um34) was altered significantly, and the Um34-containing form was substantially reduced in all tissues examined. Selenoprotein expression in these animals was most affected in tissues in which the Sec tRNA levels were most severely reduced. Importantly,mice had a neurological phenotype strikingly similar to that of mice in which the selenoprotein P gene had been removed and their life span was substantially reduced. The results indicate that STAF influences selenoprotein expression by enhancing Trsp synthesis in an organ-specific manner and by controlling Sec tRNA modification in each tissue examined.

Original languageEnglish (US)
Pages (from-to)61-71
Number of pages11
JournalBiochemical Journal
Volume418
Issue number1
DOIs
StatePublished - Feb 15 2009

Fingerprint

Activating Transcription Factors
Selenoproteins
Genes
Tissue
Transgenes
Selenoprotein P
Methylation
RNA Polymerase II
selenocysteine-tRNA
selenocysteinyl-tRNA
Liver
Transgenic Mice
Muscle
Testis
Brain
Protein Isoforms
Animals
Spleen
Binding Sites
RNA

Keywords

  • Sec tRNA gene transcription activating factor (STAF)
  • Selenium
  • Selenocysteine (Sec) tRNA gene (Trsp)
  • Selenoprotein
  • Survival rate
  • tRNA transcription

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice. / Carlson, Bradley A.; Schweizer, Ulrich; Perella, Christine; Shrimali, Rajeev Kumar; Feigenbaum, Lionel; Shen, Liya; Speransky, Svetlana; Floss, Thomas; Jeong, Soon Jeong; Watts, Jennifer; Hoffmann, Victoria; Combs, Gerald F.; Gladyshev, Vadim N.; Hatfield, Dolph L.

In: Biochemical Journal, Vol. 418, No. 1, 15.02.2009, p. 61-71.

Research output: Contribution to journalArticle

Carlson, BA, Schweizer, U, Perella, C, Shrimali, RK, Feigenbaum, L, Shen, L, Speransky, S, Floss, T, Jeong, SJ, Watts, J, Hoffmann, V, Combs, GF, Gladyshev, VN & Hatfield, DL 2009, 'The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice', Biochemical Journal, vol. 418, no. 1, pp. 61-71. https://doi.org/10.1042/BJ20081304
Carlson, Bradley A. ; Schweizer, Ulrich ; Perella, Christine ; Shrimali, Rajeev Kumar ; Feigenbaum, Lionel ; Shen, Liya ; Speransky, Svetlana ; Floss, Thomas ; Jeong, Soon Jeong ; Watts, Jennifer ; Hoffmann, Victoria ; Combs, Gerald F. ; Gladyshev, Vadim N. ; Hatfield, Dolph L. / The selenocysteine tRNA STAF-binding region is essential for adequate selenocysteine tRNA status, selenoprotein expression and early age survival of mice. In: Biochemical Journal. 2009 ; Vol. 418, No. 1. pp. 61-71.
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AU - Shrimali, Rajeev Kumar

AU - Feigenbaum, Lionel

AU - Shen, Liya

AU - Speransky, Svetlana

AU - Floss, Thomas

AU - Jeong, Soon Jeong

AU - Watts, Jennifer

AU - Hoffmann, Victoria

AU - Combs, Gerald F.

AU - Gladyshev, Vadim N.

AU - Hatfield, Dolph L.

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