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LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification

Garza, Raquel LU orcid ; Atacho, Diahann A M LU orcid ; Adami, Anita LU ; Gerdes, Patricia LU orcid ; Vinod, Meghna ; Hsieh, PingHsun ; Karlsson, Ofelia LU ; Horvath, Vivien LU orcid ; Johansson, Pia A LU and Pandiloski, Ninoslav LU orcid , et al. (2023) In Science Advances 9(44).
Abstract

The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively... (More)

The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.

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type
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publication status
published
subject
keywords
Animals, Humans, Retroelements/genetics, Transcriptome, Long Interspersed Nucleotide Elements/genetics, Neurons, Primates/genetics
in
Science Advances
volume
9
issue
44
article number
eadh9543
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • scopus:85175770022
  • pmid:37910626
ISSN
2375-2548
DOI
10.1126/sciadv.adh9543
language
English
LU publication?
yes
id
67291f8f-9975-41f0-8a5f-8478a6798ea1
date added to LUP
2023-11-13 17:02:26
date last changed
2024-04-25 19:34:09
@article{67291f8f-9975-41f0-8a5f-8478a6798ea1,
  abstract     = {{<p>The genetic mechanisms underlying the expansion in size and complexity of the human brain remain poorly understood. Long interspersed nuclear element-1 (L1) retrotransposons are a source of divergent genetic information in hominoid genomes, but their importance in physiological functions and their contribution to human brain evolution are largely unknown. Using multiomics profiling, we here demonstrate that L1 promoters are dynamically active in the developing and the adult human brain. L1s generate hundreds of developmentally regulated and cell type-specific transcripts, many that are co-opted as chimeric transcripts or regulatory RNAs. One L1-derived long noncoding RNA, LINC01876, is a human-specific transcript expressed exclusively during brain development. CRISPR interference silencing of LINC01876 results in reduced size of cerebral organoids and premature differentiation of neural progenitors, implicating L1s in human-specific developmental processes. In summary, our results demonstrate that L1-derived transcripts provide a previously undescribed layer of primate- and human-specific transcriptome complexity that contributes to the functional diversification of the human brain.</p>}},
  author       = {{Garza, Raquel and Atacho, Diahann A M and Adami, Anita and Gerdes, Patricia and Vinod, Meghna and Hsieh, PingHsun and Karlsson, Ofelia and Horvath, Vivien and Johansson, Pia A and Pandiloski, Ninoslav and Matas-Fuentes, Jon and Quaegebeur, Annelies and Kouli, Antonina and Sharma, Yogita and Jönsson, Marie E and Monni, Emanuela and Englund, Elisabet and Eichler, Evan E and Gale Hammell, Molly and Barker, Roger A and Kokaia, Zaal and Douse, Christopher H and Jakobsson, Johan}},
  issn         = {{2375-2548}},
  keywords     = {{Animals; Humans; Retroelements/genetics; Transcriptome; Long Interspersed Nucleotide Elements/genetics; Neurons; Primates/genetics}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{44}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification}},
  url          = {{http://dx.doi.org/10.1126/sciadv.adh9543}},
  doi          = {{10.1126/sciadv.adh9543}},
  volume       = {{9}},
  year         = {{2023}},
}