Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity

被引:171
作者
Denli, Ahmet M. m [1 ]
Narvaiza, Inigo [1 ]
Kerman, Bilal E. [1 ]
Pena, Monique [1 ]
Benner, Christopher [1 ]
Marchetto, Maria C. N. [1 ]
Diedrich, Jolene K. [5 ]
Aslanian, Aaron [2 ]
Ma, Jiao [3 ,6 ]
Moresco, James J. [5 ]
Moore, Lynne [1 ]
Hunter, Tony [2 ,4 ]
Saghatelian, Alan [3 ]
Gage, Fred H. [1 ,7 ,8 ]
机构
[1] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
[2] Salk Inst Biol Studies, Mol & Cell Biol Lab, La Jolla, CA 92037 USA
[3] Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA
[4] Salk Inst Biol Studies, Ctr Canc, La Jolla, CA 92037 USA
[5] Salk Inst Biol Studies, Mass Spectrometry Ctr, La Jolla, CA 92037 USA
[6] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA
[7] Univ Calif San Diego, Ctr Acad Res & Training Anthropogeny CARTA, La Jolla, CA 92093 USA
[8] Univ Calif San Diego, KIBM, La Jolla, CA 92093 USA
关键词
TRANSPOSABLE ELEMENTS; STEM-CELLS; TRANSCRIPTION; EXPRESSION; PROTEIN; RNA; IDENTIFICATION; TRANSPOSITION; TRANSLATION; DYNAMICS;
D O I
10.1016/j.cell.2015.09.025
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:583 / 593
页数:11
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