Universität zu Köln

Kurian, Leo ORCID: 0000-0001-7466-5169, Palanimurugan, R., Goedderz, Daniela and Dohmen, R. Juergen (2011). Polyamine sensing by nascent ornithine decarboxylase antizyme stimulates decoding of its mRNA. Nature, 477 (7365). S. 490 - 496. LONDON: NATURE PUBLISHING GROUP. ISSN 0028-0836

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Abstract

Polyamines are essential organic polycations with multiple cellular functions relevant for cell division, cancer and ageing(1-3). Regulation of polyamine synthesis is mainly achieved by controlling the activity of ornithine decarboxylase (ODC) through an unusual mechanism involving ODC antizyme(1,4), the binding of which disrupts homodimeric ODC and targets it for ubiquitin-independent degradation by the 26S proteasome(5). Whereas mammals express several antizyme genes(6), we have identified a single orthologue, termed OAZ1, in Saccharomyces cerevisiae(7). Similar to its mammalian counterparts, OAZ1 synthesis is induced with rising intracellular polyamine concentrations, which also inhibit ubiquitin-dependent degradation of the OAZ1 protein(7). Together, these mechanisms contribute to a homeostatic feedback regulation of polyamines(1,7,8). Antizyme synthesis involves a conserved +1 ribosomal frameshifting (RFS) event at an internal STOP codon during decoding of its messenger RNA(6-10). Here we used S. cerevisiae OAZ1 to dissect the enigmatic mechanism underlying polyamine regulation of RFS. In contrast with previous assumptions, we report here that the nascent antizyme polypeptide is the relevant polyamine sensor that operates in cis to negatively regulate upstream RFS on the polysomes, where its own mRNA is being translated. At low polyamine levels, the emerging antizyme polypeptide inhibits completion of its synthesis causing a ribosome pile-up on antizyme mRNA, whereas polyamine binding to nascent antizyme promotes completion of its synthesis. Thus, our study reveals a novel autoregulatory mechanism, in which binding of a small metabolite to a nascent sensor protein stimulates the latter's synthesis co-translationally.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kurian, Leo UNSPECIFIED orcid.org/0000-0001-7466-5169 UNSPECIFIED Palanimurugan, R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Goedderz, Daniela UNSPECIFIED UNSPECIFIED UNSPECIFIED Dohmen, R. Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-488899
DOI:	10.1038/nature10393
Journal or Publication Title:	Nature
Volume:	477
Number:	7365
Page Range:	S. 490 - 496
Date:	2011
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	0028-0836
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRANSLATION; YEAST; RIBOSOME; DEGRADATION; PATHWAY; PROTEIN; STRESS; TUNNEL Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48889