title: A dual upstream open reading frame-based autoregulatory circuit controlling polyamine-responsive translation.
abstract: A novel form of translational regulation is described for the key polyamine biosynthetic enzyme S-adenosylmethionine decarboxylase (AdoMetDC). Plant AdoMetDC mRNA 5' leaders contain two highly conserved overlapping upstream open reading frames (uORFs): the 5' tiny and 3' small uORFs. We demonstrate that the small uORF-encoded peptide is responsible for constitutively repressing downstream translation of the AdoMetDC proenzyme ORF in the absence of increased polyamine levels. This first example of a sequence-dependent uORF to be described in plants is also functional in Saccharomyces cerevisiae. The tiny uORF is required for normal polyamine-responsive AdoMetDC mRNA translation, and we propose that this is achieved by control of ribosomal recognition of the occluded small uORF, either by ribosomal leaky scanning or by programmed -1 frameshifting. In vitro expression demonstrated that both the tiny and the small uORFs are translated. This tiny/small uORF configuration is highly conserved from moss to Arabidopsis thaliana, and a more diverged tiny/small uORF arrangement is found in the AdoMetDC mRNA 5' leader of the single-celled green alga Chlamydomonas reinhardtii, indicating an ancient origin for the uORFs.
authors.affiliation: Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, United Kingdom.
authors.forename: Colin
authors.initials: C
authors.lastname: Hanfrey
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Elliott
authors.forename: Marina
authors.initials: M
authors.lastname: Franceschetti
authors.forename: Melinda J
authors.initials: MJ
authors.lastname: Mayer
authors.forename: Crista
authors.initials: C
authors.lastname: Illingworth
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Michael
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D017360:Arabidopsis / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D015317:Biogenic Polyamines / Q000378:metabolism* / Q000494:pharmacology; D016825:Chlamydomonas reinhardtii / Q000235:genetics / Q000378:metabolism; D018744:DNA, Plant / Q000235:genetics; D018506:Gene Expression Regulation, Plant / Q000187:drug effects; D006706:Homeostasis; D016366:Open Reading Frames; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018749:RNA, Plant / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D015317:Biogenic Polyamines; D018744:DNA, Plant; D012333:RNA, Messenger; D018749:RNA, Plant; D012437:Adenosylmethionine Decarboxylase