title: Programmed ribosomal frameshifting in the expression of the regulator of intestinal stem cell proliferation, adenomatous polyposis coli (APC).
abstract: 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_AA.A_AA.C in Caenorhabditids, fruit flies and the mosquitoes studied while a variant A_AA.A_AA.A 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 a 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.
authors: Biochemistry Department, University College Cork, Cork, Ireland. brave.oval.pan@gmail.com
authors: Pavel V
authors: PV
authors: Baranov
authors: Norma M
authors: NM
authors: Wills
authors: Kathy A
authors: KA
authors: Barriscale
authors: Andrew E
authors: AE
authors: Firth
authors: Molly C
authors: MC
authors: Jud
authors: Anthea
authors: A
authors: Letsou
authors: Gerard
authors: G
authors: Manning
authors: John F
authors: JF
authors: Atkins
references: EMBO J. 2003 Nov 3;22(21):5941-50
references: 14592990
references: J Biol Chem. 2006 Mar 17;281(11):7082-8
references: 16407312
references: Genome Res. 2004 Apr;14(4):708-15
references: 15060014
references: Dev Biol. 2010 Sep 15;345(2):144-55
references: 20624379
references: Proc Natl Acad Sci U S A. 1995 May 9;92(10):4482-6
references: 7753829
references: EMBO J. 2003 Sep 15;22(18):4770-8
references: 12970189
references: J Cell Sci. 2007 Oct 1;120(Pt 19):3327-35
references: 17881494
references: J Cell Sci. 2010 Mar 1;123(Pt 5):736-46
references: 20144988
references: Cell. 2009 Jul 23;138(2):366-76
references: 19632184
references: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8161-6
references: 12034871
references: New Biol. 1989 Nov;1(2):159-69
references: 2562219
references: J Mol Biol. 1994 Feb 4;235(5):1406-20
references: 8107082
references: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W135-41
references: 15215366
references: Trends Genet. 2006 Mar;22(3):174-81
references: 16460832
references: Eur J Biochem. 1998 May 1;253(3):591-7
references: 9654054
references: Curr Protoc Bioinformatics. 2010 Mar;Chapter 3:Unit 3.8.1-25
references: 20205190
references: RNA. 2003 Dec;9(12):1422-30
references: 14623998
references: Nucleic Acids Res. 2006 Jul 1;34(Web Server issue):W416-22
references: 16845039
references: Nucleic Acids Res. 2004 Feb 03;32(2):784-90
references: 14762205
references: Oncogene. 2004 Sep 16;23(42):7144-8
references: 15273719
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D211-22
references: 19920124
references: J Mol Biol. 1992 Sep 20;227(2):463-79
references: 1404364
references: Mol Cell Biol. 2001 Mar;21(6):1899-907
references: 11238926
references: J Bacteriol. 2005 Jun;187(12):4023-32
references: 15937165
references: Genome Res. 2004 May;14(5):988-95
references: 15123596
references: Nature. 1988 Jan 21;331(6153):280-3
references: 2447506
references: Nature. 1986 Jul 17-23;322(6076):273-5
references: 3736654
references: BMC Bioinformatics. 2006 Feb 16;7:75
references: 16483358
references: Virus Res. 2009 Feb;139(2):193-208
references: 18621088
references: Hum Mol Genet. 2001 Apr;10(7):721-33
references: 11257105
references: J Bacteriol. 1994 Nov;176(22):6842-51
references: 7961443
references: Curr Biol. 1999 Jan 28;9(2):105-8
references: 10021369
references: EMBO Rep. 2002 Apr;3(4):373-7
references: 11897659
references: Virol J. 2009 Feb 05;6:14
references: 19196463
references: Science. 2009 Apr 10;324(5924):218-23
references: 19213877
references: Methods Mol Biol. 2008;420:45-59
references: 18641940
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D613-9
references: 19906737
references: Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):174-8
references: 1986362
references: BMC Genomics. 2009 Jan 29;10:57
references: 19178717
references: Nucleic Acids Res. 2003 Jul 1;31(13):3406-15
references: 12824337
references: Dev Biol. 2009 Sep 15;333(2):337-47
references: 19607822
references: Nucleic Acids Res. 2008 Jan;36(1):30-40
references: 17984074
references: Nucleic Acids Res. 2007;35(1):165-74
references: 17158156
references: Cold Spring Harb Symp Quant Biol. 2001;66:233-48
references: 12762025
references: Virology. 2005 Feb 20;332(2):498-510
references: 15680415
references: J Virol. 2009 Mar;83(5):2119-29
references: 19091866
references: Bioinformatics. 2005 Feb 1;21(3):282-92
references: 15347574
references: RNA. 1998 Apr;4(4):479-86
references: 9630253
references: Genes Dev. 1997 Dec 15;11(24):3286-305
references: 9407023
references: Nucleic Acids Res. 2011 Apr;39(7):2799-808
references: 21109528
references: Nucleic Acids Res. 2008 Jan;36(Database issue):D735-40
references: 18056084
references: Genes Dev. 2004 Jun 15;18(12):1385-90
references: 15198980
references: Genome Res. 2007 Dec;17(12):1823-36
references: 17989253
references: Science. 1997 Oct 3;278(5335):120-3
references: 9311916
references: Cold Spring Harb Symp Quant Biol. 2001;66:249-58
references: 12762026
references: Nucleic Acids Res. 2007;35(16):5581-92
references: 17704133
references: Development. 2009 Jul;136(13):2255-64
references: 19502486
references: Nature. 2010 Aug 5;466(7307):720-6
references: 20686567
references: Annu Rev Cell Dev Biol. 2004;20:781-810
references: 15473860
references: RNA. 2002 Jan;8(1):16-28
references: 11871658
references: Genes Dev. 1992 Mar;6(3):511-9
references: 1547945
references: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11133-8
references: 12149516
references: Virol J. 2008 Sep 26;5:108
references: 18822126
references: J Mol Biol. 2010 Jun 11;399(3):385-96
references: 20417644
references: Nucleic Acids Res. 2010 Jan;38(Database issue):D69-74
references: 19783826
references: BMC Bioinformatics. 2008 Apr 02;9:178
references: 18384676
references: Gut. 2007 Mar;56(3):417-25
references: 16840506
references: Bioinformatics. 2006 Oct 15;22(20):2463-5
references: 16895933
references: Genome Res. 2002 Jan;12(1):198-202
references: 11779845
references: EMBO J. 2007 Jan 10;26(1):242-52
references: 17170705
references: Nucleic Acids Res. 2004 Mar 19;32(5):1792-7
references: 15034147
references: Curr Protoc Bioinformatics. 2002 Aug;Chapter 6:Unit 6.2
references: 18792942