Identification and activity of the functional complex between hnRNPL and the pseudoexfoliation syndrome-associated lncRNA, LOXL1-AS1

Hum Mol Genet. 2020 Jul 29;29(12):1986-1995. doi: 10.1093/hmg/ddaa021.

Abstract

Individuals with pseudoexfoliation (PEX) syndrome exhibit various connective tissue pathologies associated with dysregulated extracellular matrix homeostasis. PEX glaucoma is a common, aggressive form of open-angle glaucoma resulting from the deposition of fibrillary material in the conventional outflow pathway. However, the molecular mechanisms that drive pathogenesis and genetic risk remain poorly understood. PEX glaucoma-associated single-nucleotide polymorphisms are located in and affect activity of the promoter of LOXL1-AS1, a long non-coding RNA (lncRNA). Nuclear and non-nuclear lncRNAs regulate a host of biological processes, and when dysregulated, contribute to disease. Here we report that LOXL1-AS1 localizes to the nucleus where it selectively binds to the mRNA processing protein, heterogeneous nuclear ribonucleoprotein-L (hnRNPL). Both components of this complex are critical for the regulation of global gene expression in ocular cells, making LOXL1-AS1 a prime target for investigation in PEX syndrome and glaucoma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / genetics
  • Exfoliation Syndrome / genetics*
  • Exfoliation Syndrome / pathology
  • Gene Expression Regulation / genetics
  • Genetic Predisposition to Disease
  • Glaucoma, Open-Angle / genetics*
  • Glaucoma, Open-Angle / pathology
  • Humans
  • Multiprotein Complexes / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Promoter Regions, Genetic / genetics
  • RNA, Long Noncoding / genetics*
  • Ribonucleoproteins / genetics*

Substances

  • HNRNPL protein, human
  • Multiprotein Complexes
  • RNA, Long Noncoding
  • Ribonucleoproteins
  • Amino Acid Oxidoreductases
  • LOXL1 protein, human