title: A novel function of RNAs arising from the long terminal repeat of human endogenous retrovirus 9 in cell cycle arrest.
abstract: The human genome contains approximately 50 copies of the replication-defective human endogenous retrovirus 9 (ERV-9) and thousands of copies of its solitary long term repeat (sLTR) element. While some sLTRs are located upstream of critical genes and have enhancer activity, other sLTRs are located within introns and may be transcribed as RNAs. We found that intronic RNAs arising from U3 sLTRs of ERV-9 were expressed as both sense (S) and antisense (AS) transcripts in all human cells tested but that expression levels differed in malignant versus nonmalignant cells. In nonmalignant cells, AS was expressed at higher levels than S and at higher levels than in malignant cells; in malignant cells, AS was expressed at amounts equivalent to those of S RNA. Critically, U3 AS RNA was found to physically bind to key transcription factors for cellular proliferation, including NF-Y, p53, and sp1, indicating that such RNA transcripts may function as decoy targets or traps for NF-Y and thus inhibit the growth of human cancer cells. Indeed, short U3 oligodeoxynucleotides (ODNs) based on these RNA sequences ably inhibited proliferation of cancer cell lines driven by cyclins B1/B2, the gene targets of NF-Y.
authors.affiliation: Division of Therapeutic Proteins, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Xu
authors.forename: Abdel G
authors.initials: AG
authors.lastname: Elkahloun
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
authors.forename: Andrzej
authors.initials: A
authors.lastname: Grajkowski
authors.forename: Serge L
authors.initials: SL
authors.lastname: Beaucage
authors.forename: Emanuel F
authors.initials: EF
authors.lastname: Petricoin
authors.forename: Valerie
authors.initials: V
authors.lastname: Calvert
authors.forename: Hartmut
authors.initials: H
authors.lastname: Juhl
authors.forename: Frederick
authors.initials: F
authors.lastname: Mills
authors.forename: Karen
authors.initials: K
authors.lastname: Mason
authors.forename: Neal
authors.initials: N
authors.lastname: Shastri
authors.forename: Josh
authors.initials: J
authors.lastname: Chik
authors.forename: Cynthia
authors.initials: C
authors.lastname: Xu
authors.forename: Amy S
authors.initials: AS
authors.lastname: Rosenberg
mesh_terms: D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D020077:Endogenous Retroviruses / Q000472:pathogenicity*; D006801:Humans; D011485:Protein Binding; D016372:RNA, Antisense / Q000096:biosynthesis* / Q000235:genetics; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D020079:Terminal Repeat Sequences / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D016372:RNA, Antisense; D012367:RNA, Viral; D014157:Transcription Factors