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

doi:10.1016/j.cell.2015.09.025

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 journal › Article › peer-review

163 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 language	English (US)
Pages (from-to)	583-593
Number of pages	11
Journal	Cell
Volume	163
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2015.09.025
State	Published - Oct 22 2015
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2015.09.025

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title = "Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity",

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.",

author = "Denli, {Ahmet M.} and I{\~n}igo Narvaiza and Kerman, {Bilal E.} and Monique Pena and Christopher Benner and Marchetto, {Maria C.N.} and Diedrich, {Jolene K.} and Aaron Aslanian and Jiao Ma and Moresco, {James J.} and Lynne Moore and Tony Hunter and Alan Saghatelian and Gage, {Fred H.}",

note = "Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

year = "2015",

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doi = "10.1016/j.cell.2015.09.025",

language = "English (US)",

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T1 - Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity

AU - Denli, Ahmet M.

AU - Narvaiza, Iñigo

AU - Kerman, Bilal E.

AU - Pena, Monique

AU - Benner, Christopher

AU - Marchetto, Maria C.N.

AU - Diedrich, Jolene K.

AU - Aslanian, Aaron

AU - Ma, Jiao

AU - Moresco, James J.

AU - Moore, Lynne

AU - Hunter, Tony

AU - Saghatelian, Alan

AU - Gage, Fred H.

PY - 2015/10/22

Y1 - 2015/10/22

N2 - 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.

AB - 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.

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Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity

Abstract

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