Both linear and discontinuous ribosome scanning are used for translation initiation from bicistronic human immunodeficiency virus type 1 env mRNAs.
Human immunodeficiency virus type 1 (HIV-1) generates 16 alternatively spliced isoforms of env mRNA that contain the same overlapping open reading frames for Vpu and Env proteins but differ in their 5' untranslated regions (UTR). A subset of env mRNAs carry the extra upstream Rev initiation codon in the 5' UTR. We explored the effect of the alternative UTR on the translation of Vpu and Env proteins from authentic env mRNAs expressed from cDNA constructs. Vpu expression from the subset of env mRNA isoforms with exons containing an upstream Rev AUG codon was minimal. However, every env mRNA isoform expressed similar levels of Env protein. Mutations that removed, altered the strength of, or introduced upstream AUG codons dramatically altered Vpu expression but had little impact on the consistent expression of Env. These data show that the different isoforms of env mRNA are not redundant but instead regulate Vpu production in HIV-1-infected cells. Furthermore, while the initiation of Vpu translation conforms to the leaky ribosome-scanning model, the consistent Env synthesis infers a novel, discontinuous ribosome-scanning mechanism to translate Env.
Anderson
Jenny L
JL
Department of Microbiology and Immunology, The University of Melbourne, Parkville 3010, Victoria, Australia.
Johnson
Adam T
AT
Howard
Jane L
JL
Purcell
Damian F J
DF
D020121:5' Untranslated Regions / Q000235:genetics; D003001:Cloning, Molecular; D017931:DNA Primers; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000235:genetics* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics*; D054298:Human Immunodeficiency Virus Proteins; D015151:Immunoblotting; D016296:Mutagenesis; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics* / Q000378:metabolism; D000086082:Viroporin Proteins
D020121:5' Untranslated Regions; D017931:DNA Primers; D015686:Gene Products, env; D054298:Human Immunodeficiency Virus Proteins; D012333:RNA, Messenger; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins