eLife (Jan 2023)

MicroRNA-eQTLs in the developing human neocortex link miR-4707-3p expression to brain size

  • 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

DOI
https://doi.org/10.7554/eLife.79488
Journal volume & issue
Vol. 12

Abstract

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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.

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