Abstract
For recognition by the translational machinery, most eukaryotic cellular mRNAs have a 5' cap structure [e.g. m7G(5')ppp(5')N]. We describe a translation enhancer sequence (3'TE) located in the 3'-untranslated region (UTR) of the genome of the PAV barley yellow dwarf virus (BYDV-PAV) which stimulates translation from uncapped mRNA by 30- to 100-fold in vitro and in vivo to a level equal to that of efficient capped mRNAs. A four base duplication within the 3'TE destroyed the stimulatory activity. Efficient translation was recovered by addition of a 5' cap to this mRNA. Translation of both uncapped mRNA containing the 3'TE in cis and capped mRNA lacking any BYDV-PAV sequence was inhibited specifically by added 3'TE RNA in trans. This inhibition was reversed by adding initiation factor 4F (eIF4F), suggesting that the 3'TE, like the 5' cap, mediates eIF4F-dependent translation initiation. The BYDV-PAV 5'UTR was necessary for the 3'TE to function, except when the 3'TE itself was moved to the 5'UTR. Thus, the 3'TE is sufficient for recruiting the translation factors and ribosomes, while the viral 5'UTR may serve only for the long distance 3'-5' communication. Models are proposed to explain this novel mechanism of cap-independent translation initiation facilitated by the 3'UTR.
MeSH Terms
Conserved Sequence
Eukaryotic Initiation Factor-4F
Genome, Viral
Introns
Luteovirus/genetics
Peptide Initiation Factors/metabolism,pharmacology
Protein Biosynthesis
RNA Caps
RNA, Messenger/metabolism
RNA, Viral/metabolism
Chemicals
Eukaryotic Initiation Factor-4F
Peptide Initiation Factors
RNA Caps
RNA, Messenger
RNA, Viral
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wang S
Molecular, Cellular and Developmental Biology Program, Iowa State University, Ames 50011, USA.
Browning K S
Miller W A
References (29)
29 references, click to expand
-
Translational regulation in development.
Cell. 1995 Apr 21;81(2):171-8
PMID: 7736569
-
Internal ribosome entry site within hepatitis C virus RNA.
J Virol. 1992 Mar;66(3):1476-83
PMID: 1310759
-
Barley yellow dwarf viruses.
Annu Rev Phytopathol. 1997;35:167-90
PMID: 15012520
-
Internal initiation of translation in eukaryotes: the picornavirus paradigm and beyond.
RNA. 1995 Dec;1(10):985-1000
PMID: 8595564
-
Sequence and organization of barley yellow dwarf virus genomic RNA.
Nucleic Acids Res. 1988 Jul 11;16(13):6097-111
PMID: 3399386
-
Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA.
Cell. 1992 Jan 10;68(1):119-31
PMID: 1310072
-
RNA pseudoknot domain of tobacco mosaic virus can functionally substitute for a poly(A) tail in plant and animal cells.
Genes Dev. 1990 Jul;4(7):1149-57
PMID: 1976569
-
Association of the yeast poly(A) tail binding protein with translation initiation factor eIF-4G.
EMBO J. 1996 Dec 16;15(24):7168-77
PMID: 9003792
-
A phylogenetically conserved sequence within viral 3' untranslated RNA pseudoknots regulates translation.
Mol Cell Biol. 1993 Sep;13(9):5331-47
PMID: 8355685
-
The complete nucleotide sequence and genome organization of red clover necrotic mosaic virus RNA-1.
Virology. 1989 Aug;171(2):543-54
PMID: 2763465
-
A sequence located 4.5 to 5 kilobases from the 5' end of the barley yellow dwarf virus (PAV) genome strongly stimulates translation of uncapped mRNA.
J Biol Chem. 1995 Jun 2;270(22):13446-52
PMID: 7768947
-
Eukaryotic protein synthesis: an in vitro analysis.
Biochimie. 1994;76(9):822-30
PMID: 7880898
-
Identity of the 5'-terminal RNA nucleotide sequence of the satellite tobacco necrosis virus and its helper virus: possible role of the 5'-terminus in the recognition by virus-specific RNA replicase.
Proc Natl Acad Sci U S A. 1970 May;66(1):140-5
PMID: 5273892
-
Genes and cis-acting sequences involved in replication of barley yellow dwarf virus-PAV RNA.
Virology. 1995 Sep 10;212(1):186-95
PMID: 7676628
-
The absence of a m7G cap on beta-globin mRNA and alfalfa mosaic virus RNA 4 increases the amounts of initiation factor 4F required for translation.
J Biol Chem. 1990 Nov 15;265(32):19582-7
PMID: 2246243
-
Cap-independent enhancement of translation by a plant potyvirus 5' nontranslated region.
J Virol. 1990 Apr;64(4):1590-7
PMID: 2319646
-
The histone 3'-terminal stem-loop is necessary for translation in Chinese hamster ovary cells.
Nucleic Acids Res. 1996 May 15;24(10):1954-62
PMID: 8657580
-
RNA recognition and translational regulation by a homeodomain protein.
Nature. 1996 Feb 22;379(6567):694-9
PMID: 8602214
-
Deadenylation of the unstable mRNA encoded by the yeast MFA2 gene leads to decapping followed by 5'-->3' digestion of the transcript.
Genes Dev. 1994 Apr 1;8(7):855-66
PMID: 7926773
-
Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA.
Nature. 1988 Jul 28;334(6180):320-5
PMID: 2839775
-
Sequence variability in the genome-3'-terminal region of BYDV for 10 geographically distinct PAV-like isolates of barley yellow dwarf virus: analysis of the ORF6 variation.
Arch Virol. 1994;139(3-4):403-16
PMID: 7832645
-
Canonical eukaryotic initiation factors determine initiation of translation by internal ribosomal entry.
Mol Cell Biol. 1996 Dec;16(12):6859-69
PMID: 8943341
-
The 3' untranslated region of satellite tobacco necrosis virus RNA stimulates translation in vitro.
Mol Cell Biol. 1993 Jun;13(6):3340-9
PMID: 8497255
-
Selective translation initiation by ribosome jumping in adenovirus-infected and heat-shocked cells.
Genes Dev. 1996 Jun 15;10(12):1557-67
PMID: 8666238
-
Polyadenylation of c-mos mRNA as a control point in Xenopus meiotic maturation.
Nature. 1995 Apr 6;374(6522):511-6
PMID: 7700377
-
Isolation and characterization of the 102-kilodalton RNA-binding protein that binds to the 5' and 3' translational enhancers of tobacco mosaic virus RNA.
J Biol Chem. 1996 Jun 14;271(24):14316-22
PMID: 8663059
-
Control of start codon choice on a plant viral RNA encoding overlapping genes.
Plant Cell. 1993 Jun;5(6):679-92
PMID: 8329899
-
The cap and poly(A) tail function synergistically to regulate mRNA translational efficiency.
Genes Dev. 1991 Nov;5(11):2108-16
PMID: 1682219
-
Regulation of translation by specific protein/mRNA interactions.
Biochimie. 1994;76(9):867-79
PMID: 7880904