MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size
Expression quantitative trait loci (eQTL) data have proven important for linking non-coding loci to protein-coding genes. But eQTL studies rarely measure microRNAs (miRNAs), small non-coding RNAs known to play a role in human brain development and neurogenesis. Here, we performed small-RNA sequencin...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/79488 |
| _version_ | 1797946579028541440 |
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| author | Michael J Lafferty Nil Aygün Niyanta K Patel Oleh Krupa Dan Liang Justin M Wolter Daniel H Geschwind Luis de la Torre-Ubieta Jason L Stein |
| author_facet | Michael J Lafferty Nil Aygün Niyanta K Patel Oleh Krupa Dan Liang Justin M Wolter Daniel H Geschwind Luis de la Torre-Ubieta Jason L Stein |
| author_sort | Michael J Lafferty |
| collection | DOAJ |
| description | Expression quantitative trait loci (eQTL) data have proven important for linking non-coding loci to protein-coding genes. But eQTL studies rarely measure microRNAs (miRNAs), small non-coding RNAs known to play a role in human brain development and neurogenesis. Here, we performed small-RNA sequencing across 212 mid-gestation human neocortical tissue samples, measured 907 expressed miRNAs, discovering 111 of which were novel, and identified 85 local-miRNA-eQTLs. Colocalization of miRNA-eQTLs with GWAS summary statistics yielded one robust colocalization of miR-4707–3p expression with educational attainment and brain size phenotypes, where the miRNA expression increasing allele was associated with decreased brain size. Exogenous expression of miR-4707–3p in primary human neural progenitor cells decreased expression of predicted targets and increased cell proliferation, indicating miR-4707–3p modulates progenitor gene regulation and cell fate decisions. Integrating miRNA-eQTLs with existing GWAS yielded evidence of a miRNA that may influence human brain size and function via modulation of neocortical brain development. |
| first_indexed | 2024-04-10T21:14:21Z |
| format | Article |
| id | doaj.art-879e6be524424938b8ce9bf78a43c091 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-10T21:14:21Z |
| publishDate | 2023-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-879e6be524424938b8ce9bf78a43c0912023-01-20T13:52:52ZengeLife Sciences Publications LtdeLife2050-084X2023-01-011210.7554/eLife.79488MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain sizeMichael J Lafferty0https://orcid.org/0000-0002-1000-0480Nil Aygün1Niyanta K Patel2Oleh Krupa3Dan Liang4Justin M Wolter5Daniel H Geschwind6https://orcid.org/0000-0003-2896-3450Luis de la Torre-Ubieta7Jason L Stein8https://orcid.org/0000-0003-4829-0513Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, United States; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, United States; Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, United StatesNeurogenetics Program, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Center for Autism Research and Treatment, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Department of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, United States; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, United States; Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, United StatesExpression quantitative trait loci (eQTL) data have proven important for linking non-coding loci to protein-coding genes. But eQTL studies rarely measure microRNAs (miRNAs), small non-coding RNAs known to play a role in human brain development and neurogenesis. Here, we performed small-RNA sequencing across 212 mid-gestation human neocortical tissue samples, measured 907 expressed miRNAs, discovering 111 of which were novel, and identified 85 local-miRNA-eQTLs. Colocalization of miRNA-eQTLs with GWAS summary statistics yielded one robust colocalization of miR-4707–3p expression with educational attainment and brain size phenotypes, where the miRNA expression increasing allele was associated with decreased brain size. Exogenous expression of miR-4707–3p in primary human neural progenitor cells decreased expression of predicted targets and increased cell proliferation, indicating miR-4707–3p modulates progenitor gene regulation and cell fate decisions. Integrating miRNA-eQTLs with existing GWAS yielded evidence of a miRNA that may influence human brain size and function via modulation of neocortical brain development.https://elifesciences.org/articles/79488miRNAeQTLneurogenesis |
| spellingShingle | Michael J Lafferty Nil Aygün Niyanta K Patel Oleh Krupa Dan Liang Justin M Wolter Daniel H Geschwind Luis de la Torre-Ubieta Jason L Stein MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size eLife miRNA eQTL neurogenesis |
| title | MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size |
| title_full | MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size |
| title_fullStr | MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size |
| title_full_unstemmed | MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size |
| title_short | MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size |
| title_sort | microrna eqtls in the developing human neocortex link mir 4707 3p expression to brain size |
| topic | miRNA eQTL neurogenesis |
| url | https://elifesciences.org/articles/79488 |
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