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

Autor: Garza R; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA., Atacho DAM; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA., Adami A; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA., Gerdes P; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden., Vinod M; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden., Hsieh P; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA.; Department of Genetics, Cell Biology, and Development, University of Minnesota Medical School, Minneapolis, MN, 55455, USA., Karlsson O; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden., Horvath V; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden., Johansson PA; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden., Pandiloski N; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.; Epigenetics and Chromatin Dynamics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC B11, Lund University, 221 84 Lund, Sweden., Matas-Fuentes J; Epigenetics and Chromatin Dynamics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC B11, Lund University, 221 84 Lund, Sweden., Quaegebeur A; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.; Department of Clinical Neurosciences, University of Cambridge and Department of Pathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Kouli A; Department of Clinical Neuroscience and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, John van Geest Centre for Brain Repair, Cambridge CB2 0PY, UK., Sharma Y; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden., Jönsson ME; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden., Monni E; Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, Lund University, SE-22184 Lund, Sweden., Englund E; Department of Clinical Sciences Lund, Division of Pathology, Lund University, Lund, Sweden., Eichler EE; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, 98195, USA.; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA., Gale Hammell M; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.; Institute for Systems Genetics, Department of Neuroscience and Physiology, NYU Langone Health, New York, NY 10016, USA.; Neuroscience Institute, NYU Grossman School of Medicine, New York, NY 10016, USA., Barker RA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.; Department of Clinical Neuroscience and Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, John van Geest Centre for Brain Repair, Cambridge CB2 0PY, UK., Kokaia Z; Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, Lund University, SE-22184 Lund, Sweden., Douse CH; Epigenetics and Chromatin Dynamics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC B11, Lund University, 221 84 Lund, Sweden., Jakobsson J; Laboratory of Molecular Neurogenetics, Department of Experimental Medical Science, Wallenberg Neuroscience Center and Lund Stem Cell Center, BMC A11, Lund University, 221 84 Lund, Sweden.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD, 20815, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 Nov 03; Vol. 9 (44), pp. eadh9543. Date of Electronic Publication: 2023 Nov 01.
DOI: 10.1126/sciadv.adh9543
Abstrakt: 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.
Databáze: MEDLINE