LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification
(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.
(Less)
- author
- organization
-
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- Molecular Neurogenetics (research group)
- Wallenberg Neuroscience Centre, Lund
- Stem Cell Center
- Cell and Gene Therapy Core
- Epigenetics and Chromatin Dynamics (research group)
- Developmental and Regenerative Neurobiology (research group)
- Stem Cells & Restorative Neurology (research group)
- Neural stem cell biology and therapy (research group)
- Neurology, Lund
- Pathology, Lund
- LUCC: Lund University Cancer Centre
- publishing date
- 2023-11-03
- type
- Contribution to journal
- 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}}, }