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Baranov, PV,Wills, NM,Barriscale, KA,Firth, AE,Jud, MC,Letsou, A,Manning, G,Atkins, JF;
2011
January
RNA biology
Programmed ribosomal frameshifting in the expression of the regulator of intestinal stem cell proliferation, adenomatous polyposis coli (APC)
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adenomatous polyposis coli programmed ribosomal frameshifting recoding RNA pseudoknot translational control alternative decoding OVERLAPPING CODING SEQUENCES WNT SIGNALING PATHWAY TUMOR-SUPPRESSOR ESCHERICHIA-COLI SACCHAROMYCES-CEREVISIAE RECODING SIGNALS RNA PSEUDOKNOTS SEAM CELLS WEB SERVER IN-VIVO
8
637
647
A programmed ribosomal frameshift (PRF) in the decoding of APC (adenomatous polyposis coli) mRNA has been identified and characterized in Caenorhabditis worms, Drosophila and mosquitoes. The frameshift product lacks the C-terminal approximately one-third of the product of standard decoding and instead has a short sequence encoded by the -1 frame which is just 13 residues in C. elegans, but is 125 in D. melanogaster. The frameshift site is A AAA AAC in Caenorhabditids, fruit flies and the mosquitoes studied while a variant A AAA AAA is found in some other nematodes. The predicted secondary RNA structure of the downstream stimulators varies considerably in the species studied. In the twelve sequenced Drosophila genomes, it is a long stem with a four-way junction in its loop. In the five sequenced Caenorhabditis species, it is a short RNA pseudoknot with an additional stem in loop 1. The efficiency of frameshifting varies significantly, depending on the particular stimulator within the frameshift cassette, when tested with reporter constructs in rabbit reticulocyte lysates. Phylogenetic analysis of the distribution of APC programmed ribosomal frameshifting cassettes suggests it has an ancient origin and raises questions about the possibility of synthesis of alternative protein products during expression of APC in other organisms such as humans. The origin of APC as a PRF candidate emerged from a prior study of evolutionary signatures derived from comparative analysis of the 12 fly genomes. Three other proposed PRF candidates (Xbp1, CG32736, CG14047) with switches in conservation of reading frames are likely explained by mechanisms other than PRF.
DOI 10.4161/rna.8.4.15395
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