RTE and CTE mRNA export elements synergistically increase expression of unstable, Rev-dependent HIV and SIV mRNAs.
Studies of retroviral mRNA export identified two distinct RNA export elements utilizing conserved eukaryotic mRNA export mechanism(s), namely the Constitutive Transport Element (CTE) and the RNA Transport Element (RTE). Although RTE and CTE are potent in nucleocytoplasmic mRNA transport and expression, neither element is as powerful as the Rev-RRE posttranscriptional control. Here, we found that whereas CTE and the up-regulatory mutant RTEm26 alone increase expression from a subgenomic gag and env clones, the combination of these elements led to a several hundred-fold, synergistic increase. The use of the RTEm26-CTE combination is a simple way to increase expression of poorly expressed retroviral genes to levels otherwise only achieved via more cumbersome RNA optimization. The potent RTEm26-CTE element could be useful in lentiviral gene therapy vectors, DNA-based vaccine vectors, and gene transfer studies of other poorly expressed genes.
Smulevitch
Sergey
S
Human Retrovirus Pathogenesis Section, National Cancer Institute-Frederick, MD 21702-1201, USA. smulevit@hotmail.com
Bear
Jenifer
J
Alicea
Candido
C
Rosati
Margherita
M
Jalah
Rashmi
R
Zolotukhin
Andrei S
AS
von Gegerfelt
Agneta
A
Michalowski
Daniel
D
Moroni
Christoph
C
Pavlakis
George N
GN
Felber
Barbara K
BK
D000818:Animals; D001692:Biological Transport; D002417:Cattle; D002460:Cell Line; D015694:Gene Products, rev / Q000378:metabolism*; D015752:Genes, env; D013006:Growth Hormone / Q000235:genetics; D006678:HIV / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D034443:RNA Transport / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D020079:Terminal Repeat Sequences; D014162:Transfection; D054321:rev Gene Products, Human Immunodeficiency Virus
D015694:Gene Products, rev; D012333:RNA, Messenger; D012367:RNA, Viral; D054321:rev Gene Products, Human Immunodeficiency Virus; D013006:Growth Hormone