EFFICIENCY OF REINITIATION OF TRANSLATION ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MESSENGER-RNAS IS DETERMINED BY THE LENGTH OF THE UPSTREAM OPEN READING FRAME AND BY INTERCISTRONIC DISTANCE

被引:142
作者
LUUKKONEN, BGM [1 ]
TAN, W [1 ]
SCHWARTZ, S [1 ]
机构
[1] KAROLINSKA INST,CTR MICROBIOL & TUMORBIOL,S-17177 STOCKHOLM,SWEDEN
关键词
D O I
10.1128/JVI.69.7.4086-4094.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
In this study, we examined the mechanism of translation of the human immunodeficiency virus type 1 tat mRNA in eucaryotic cells. This mRNA contains the tat open reading frame (ORF), followed by rev and nef ORFs, but only the first ORF, encoding tat, is efficiently translated. Introduction of premature stop codons in the tat ORF resulted in efficient translation of the downstream rev ORF. We show that the degree of inhibition of translation of rev is proportional to the Length of the upstream tat ORF. An upstream ORF spanning 84 nucleotides was predicted to inhibit 50% of the ribosomes from initiating translation at downstream AUGs. Interestingly, the distance between the upstream ORF and the start codon of the second ORF also played a role in efficiency of downstream translation initiation. It remains to be investigated if these conclusions relate to translation of mRNAs other than human immunodeficiency virus type 1 mRNAs. The strong inhibition of rev translation exerted by the presence of the tat ORF may reflect the different roles of Tat and Rev in the viral life cycle. Tat acts early to induce high production of all viral mRNAs. Rev induces a switch from the early to the late phase of the viral life cycle, resulting in production of viral structural proteins and virions. Premature Rev production may result in entrance into the late phase in the presence of suboptimal levels of viral mRNAs coding for structural proteins, resulting in inefficient virus production.
引用
收藏
页码:4086 / 4094
页数:9
相关论文
共 59 条
[1]   EXPRESSION OF DICISTRONIC TRANSCRIPTIONAL UNITS IN TRANSGENIC TOBACCO [J].
ANGENON, G ;
UOTILA, J ;
KURKELA, SA ;
TEERI, TH ;
BOTTERMAN, J ;
VANMONTAGU, M ;
DEPICKER, A .
MOLECULAR AND CELLULAR BIOLOGY, 1989, 9 (12) :5676-5684
[3]   POSTTRANSCRIPTIONAL TRANSACTIVATION IN CAULIFLOWER MOSAIC-VIRUS [J].
BONNEVILLE, JM ;
SANFACON, H ;
FUTTERER, J ;
HOHN, T .
CELL, 1989, 59 (06) :1135-1143
[4]   TRANSLATION OF EQUINE INFECTIOUS-ANEMIA VIRUS BICISTRONIC TAT-REV MESSENGER-RNA REQUIRES LEAKY RIBOSOME SCANNING OF THE TAT CTG INITIATION CODON [J].
CARROLL, R ;
DERSE, D .
JOURNAL OF VIROLOGY, 1993, 67 (03) :1433-1440
[5]   IDENTIFICATION AND EXPRESSION OF A HUMAN CYTOMEGALO-VIRUS EARLY GLYCOPROTEIN [J].
CHANG, CP ;
VESOLE, DH ;
NELSON, J ;
OLDSTONE, MBA ;
STINSKI, MF .
JOURNAL OF VIROLOGY, 1989, 63 (08) :3330-3337
[6]   MECHANISM OF ACTION OF REGULATORY PROTEINS ENCODED BY COMPLEX RETROVIRUSES [J].
CULLEN, BR .
MICROBIOLOGICAL REVIEWS, 1992, 56 (03) :375-394
[7]   HUMAN PAPILLOMAVIRUS-1A COMPLETE DNA-SEQUENCE - A NOVEL TYPE OF GENOME ORGANIZATION AMONG PAPOVAVIRIDAE [J].
DANOS, O ;
KATINKA, M ;
YANIV, M .
EMBO JOURNAL, 1982, 1 (02) :231-236
[8]  
DAYTON AI, 1988, J ACQ IMMUN DEF SYND, V1, P441
[9]   TRANSLATIONAL INHIBITION MEDIATED BY A SHORT UPSTREAM OPEN READING FRAME IN THE HUMAN CYTOMEGALOVIRUS GPUL4 (GP48) TRANSCRIPT [J].
DEGNIN, CR ;
SCHLEISS, MR ;
CAO, JH ;
GEBALLE, AP .
JOURNAL OF VIROLOGY, 1993, 67 (09) :5514-5521
[10]   THE REV GENE-PRODUCT OF THE HUMAN IMMUNODEFICIENCY VIRUS AFFECTS ENVELOPE-SPECIFIC RNA LOCALIZATION [J].
EMERMAN, M ;
VAZEUX, R ;
PEDEN, K .
CELL, 1989, 57 (07) :1155-1165