Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity

Ahmet M. Denli, Iñigo Narvaiza, Bilal E. Kerman, Monique Pena, Christopher Benner, Maria C.N. Marchetto, Jolene K. Diedrich, Aaron Aslanian, Jiao Ma, James J. Moresco, Lynne Moore, Tony Hunter, Alan Saghatelian, Fred H. Gage

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Summary LINE-1 retrotransposons are fast-evolving mobile genetic entities that play roles in gene regulation, pathological conditions, and evolution. Here, we show that the primate LINE-1 5′UTR contains a primate-specific open reading frame (ORF) in the antisense orientation that we named ORF0. The gene product of this ORF localizes to promyelocytic leukemia-adjacent nuclear bodies. ORF0 is present in more than 3,000 loci across human and chimpanzee genomes and has a promoter and a conserved strong Kozak sequence that supports translation. By virtue of containing two splice donor sites, ORF0 can also form fusion proteins with proximal exons. ORF0 transcripts are readily detected in induced pluripotent stem (iPS) cells from both primate species. Capped and polyadenylated ORF0 mRNAs are present in the cytoplasm, and endogenous ORF0 peptides are identified upon proteomic analysis. Finally, ORF0 enhances LINE-1 mobility. Taken together, these results suggest a role for ORF0 in retrotransposon-mediated diversity.

Original languageEnglish (US)
Pages (from-to)583-593
Number of pages11
JournalCell
Volume163
Issue number3
DOIs
StatePublished - Oct 22 2015
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Denli, A. M., Narvaiza, I., Kerman, B. E., Pena, M., Benner, C., Marchetto, M. C. N., Diedrich, J. K., Aslanian, A., Ma, J., Moresco, J. J., Moore, L., Hunter, T., Saghatelian, A., & Gage, F. H. (2015). Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity. Cell, 163(3), 583-593. https://doi.org/10.1016/j.cell.2015.09.025