Polyamine-Regulated translation of spermidine/spermine-N1-Acetyltransferase

Oscar Perez-Leal, Carlos A. Barrero, Allen B. Clarkson, Robert A Casero, Salim Merali

Research output: Contribution to journalArticle

Abstract

Rapid synthesis of the polyamine catabolic enzyme spermidine/spermine-N1-acetyltransferase (SSAT) in response to increased polyamines is an important polyamine homeostatic mechanism. Indirect evidence has suggested that there is an important control mechanism involving the release of a translational repressor protein that allows the immediate initiation of SSAT protein synthesis without RNA transcription, maturation, or translocation. To identify a repressor protein, we used a mass spectroscopy-based RNA-protein interaction system and found six proteins that bind to the coding region of SSAT mRNA. Individual small interfering RNA (siRNA) experiments showed that nucleolin knockdown enhances SSAT translation. Nucleolin exists in several isoforms, and we report that the isoform that binds to SSAT mRNA undergoes autocatalysis in the presence of polyamines, a result suggesting that there is a negative feedback system that helps control the cellular content of polyamines. Preliminary molecular interaction data show that a nucleolin isoform binds to a 5' stem-loop of the coding region of SSAT mRNA. The glycine/arginine-rich C terminus of nucleolin is required for binding, and the four RNA recognition motif domains are included in the isoform that blocks SSAT translation. Understanding SSAT translational control mechanisms has the potential for the development of therapeutic strategies against cancer and obesity.

Original languageEnglish (US)
Pages (from-to)1453-1467
Number of pages15
JournalMolecular and Cellular Biology
Volume32
Issue number8
DOIs
StatePublished - Apr 2012

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Spermine
Polyamines
Protein Isoforms
Repressor Proteins
Messenger RNA
RNA
Proteins
diamine N-acetyltransferase
Glycine
Small Interfering RNA
Arginine
Mass Spectrometry
Obesity
nucleolin
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Polyamine-Regulated translation of spermidine/spermine-N1-Acetyltransferase. / Perez-Leal, Oscar; Barrero, Carlos A.; Clarkson, Allen B.; Casero, Robert A; Merali, Salim.

In: Molecular and Cellular Biology, Vol. 32, No. 8, 04.2012, p. 1453-1467.

Research output: Contribution to journalArticle

Perez-Leal, Oscar ; Barrero, Carlos A. ; Clarkson, Allen B. ; Casero, Robert A ; Merali, Salim. / Polyamine-Regulated translation of spermidine/spermine-N1-Acetyltransferase. In: Molecular and Cellular Biology. 2012 ; Vol. 32, No. 8. pp. 1453-1467.
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