A nascent peptide signal responsive to endogenous levels of polyamines acts to stimulate regulatory frameshifting on antizyme mRNA.

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dc.contributor.authorYordanova, Martina M.
dc.contributor.authorWu, Cheng
dc.contributor.authorAndreev, Dmitry E.
dc.contributor.authorSachs, Matthew S.
dc.contributor.authorAtkins, John F.
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderNational Institutes of Healthen
dc.date.accessioned2018-03-29T09:34:46Z
dc.date.available2018-03-29T09:34:46Z
dc.date.issued2015-05-21
dc.date.updated2018-03-29T09:28:58Z
dc.description.abstractThe protein antizyme is a negative regulator of cellular polyamine concentrations from yeast to mammals. Synthesis of functional antizyme requires programmed +1 ribosomal frameshifting at the 3' end of the first of two partially overlapping ORFs. The frameshift is the sensor and effector in an autoregulatory circuit. Except for Saccharomyces cerevisiae antizyme mRNA, the frameshift site alone only supports low levels of frameshifting. The high levels usually observed depend on the presence of cis-acting stimulatory elements located 5' and 3' of the frameshift site. Antizyme genes from different evolutionary branches have evolved different stimulatory elements. Prior and new multiple alignments of fungal antizyme mRNA sequences from the Agaricomycetes class of Basidiomycota show a distinct pattern of conservation 5' of the frameshift site consistent with a function at the amino acid level. As shown here when tested in Schizosaccharomyces pombe and mammalian HEK293T cells, the 5' part of this conserved sequence acts at the nascent peptide level to stimulate the frameshifting, without involving stalling detectable by toe-printing. However, the peptide is only part of the signal. The 3' part of the stimulator functions largely independently and acts at least mostly at the nucleotide level. When polyamine levels were varied, the stimulatory effect was seen to be especially responsive in the endogenous polyamine concentration range, and this effect may be more general. A conserved RNA secondary structure 3' of the frameshift site has weaker stimulatory and polyamine sensitizing effects on frameshifting.en
dc.description.sponsorshipNational Institutes of Health (Grant GM068087)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationYordanova, M. M., Wu, C., Andreev, D. E., Sachs, M. S. and Atkins, J. F. (2015) 'A Nascent Peptide Signal Responsive to Endogenous Levels of Polyamines Acts to Stimulate Regulatory Frameshifting on Antizyme mRNA', Journal of Biological Chemistry, 290(29), pp. 17863-17878. doi: 10.1074/jbc.M115.647065en
dc.identifier.doi10.1074/jbc.M115.647065
dc.identifier.endpage17878en
dc.identifier.issn0021-9258
dc.identifier.issued29en
dc.identifier.journaltitleThe Journal of Biological Chemistryen
dc.identifier.startpage17863en
dc.identifier.urihttps://hdl.handle.net/10468/5717
dc.identifier.volume290en
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.urihttp://www.jbc.org/content/290/29/17863.abstract
dc.rights© 2015 by The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice—Final version free via Creative Commons CC-BY license.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectmRNAen
dc.subjectPolyamineen
dc.subjectRibosomeen
dc.subjectRNA structureen
dc.subjectTranslation regulationen
dc.subjectORFen
dc.subjectAntizymeen
dc.subjectFrameshiftingen
dc.titleA nascent peptide signal responsive to endogenous levels of polyamines acts to stimulate regulatory frameshifting on antizyme mRNA.en
dc.typeArticle (peer-reviewed)en
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