The leader of human immunodeficiency virus type 1 genomic RNA harbors an internal ribosome entry segment that is active during the G2/M phase of the cell cycle.
The 5' leader of the human immunodeficiency virus type 1 (HIV-1) genomic RNA contains highly structured domains involved in key steps of the viral life cycle. These RNA domains inhibit cap-dependent protein synthesis. Here we report that the HIV-1 5' leader harbors an internal ribosome entry site (IRES) capable of driving protein synthesis during the G(2)/M cell cycle phase in which cap-dependent initiation is inhibited. The HIV-1 IRES was delineated with bicistronic mRNAs in in vitro and ex vivo assays. The HIV-1 leader IRES spans nucleotides 104 to 336 and partially overlaps the major determinants of genomic RNA packaging. These data strongly suggest that, as for HIV-1 transcription, IRES-mediated translation initiation could play an important role in virus replication during virus-induced G(2)/M cell cycle arrest.
Brasey
Ann
A
Biochemistry Department, McGill University, H3G 1Y6 Montréal, Canada.
Lopez-Lastra
Marcelo
M
Ohlmann
Theophile
T
Beerens
Nancy
N
Berkhout
Ben
B
Darlix
Jean-Luc
JL
Sonenberg
Nahum
N
D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D039603:Eukaryotic Initiation Factor-4G / Q000378:metabolism; D016195:G2 Phase; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation; D014176:Protein Biosynthesis; D012367:RNA, Viral / Q000235:genetics*; D012270:Ribosomes / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
D020121:5' Untranslated Regions; D004279:DNA, Viral; D039603:Eukaryotic Initiation Factor-4G; D012367:RNA, Viral