Controlling human immunodeficiency virus type 1 gene expression by unnatural peptides.
Small unnatural peptides that target specific RNA structures have the potential to control biological processes. RNA-protein interactions are important in many cellular functions, including transcription, RNA splicing, and translation. One example of such interactions is the mechanism of trans-activation of human immunodeficiency virus type 1 (HIV-1) gene expression that requires the interaction of Tat protein with the trans-activation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end of all nascent HIV-1 transcripts. We report here a synthetic peptide derived from Tat sequence (37-72), containing all D-amino acids, that binds in the major groove of TAR RNA and interferes with transcriptional activation by Tat protein in vitro and in HeLa cells. Our results indicate that unnatural peptides can inhibit the transcription of specific genes regulated by RNA-protein interactions.
Huq
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Department of Pharmacology, Robert Wood Johnson Medical School, Molecular Biosciences Graduate Program, Rutgers University, Piscataway, New Jersey 08854, USA.
Ping
Y H
YH
Tamilarasu
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Rana
T M
TM
D000595:Amino Acid Sequence; D001667:Binding, Competitive / Q000235:genetics; D002474:Cell-Free System / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D012367:RNA, Viral / Q000235:genetics; D013237:Stereoisomerism; D015533:Transcriptional Activation / Q000187:drug effects; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D010455:Peptides; D020033:Protein Isoforms; D012367:RNA, Viral; D054322:tat Gene Products, Human Immunodeficiency Virus