The RNA-binding protein LIN28 controls progenitor and neuronal cell fate during postnatal neurogenesis

FASEB J. 2019 Mar;33(3):3291-3303. doi: 10.1096/fj.201801118R. Epub 2018 Nov 13.

Abstract

The RNA-binding protein LIN28 is known to regulate cell fate, tissue growth, and pluripotency; however, a unified understanding of its role at the cellular level has not been achieved. Here, we address its developmental activity in mammalian postnatal neurogenesis. Constitutive expression of LIN28 in progenitor cells of the mouse subventricular zone (SVZ) caused several distinct effects: 1) the number of differentiated neurons in the olfactory bulb was dramatically reduced, whereas the relative abundance of 2 neuronal subtypes was significantly altered, 2) the population of proliferating neural progenitors in the SVZ was reduced, whereas the proportion of neuroblasts was increased, and 3) the number of astrocytes was reduced, occasionally causing them to appear early. Thus, LIN28 acts at a poststem cell/predifferentiation step, and its continuous expression caused a precocious phenotype unlike in other experimental systems. Furthermore, for the first time in a vertebrate system, we separate the majority of the biologic role of LIN28 from its known activity of blocking the microRNA let-7 by using a circular RNA sponge. We find that although LIN28 has a multifaceted role in the number and types of cells produced during postnatal neurogenesis, it appears that its action through let-7 is responsible for only a fraction of these effects.-Romer-Seibert, J. S., Hartman, N. W., Moss, E. G. The RNA-binding protein LIN28 controls progenitor and neuronal cell fate during postnatal neurogenesis.

Keywords: circRNA; developmental timing; let-7.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Aging / pathology
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism
  • Cell Count
  • Cell Differentiation
  • Cell Line
  • Gene Expression Regulation, Developmental
  • Lateral Ventricles / cytology
  • Lateral Ventricles / metabolism
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Models, Neurological
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurogenesis / physiology*
  • Neurons / cytology*
  • Neurons / metabolism*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / metabolism
  • RNA / genetics
  • RNA / metabolism
  • RNA, Circular
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • Lin-28 protein, mouse
  • MicroRNAs
  • RNA, Circular
  • RNA-Binding Proteins
  • mirnlet7 microRNA, mouse
  • RNA