ZFIN ID: ZDB-PUB-200528-12
MKRN2 Physically Interacts with GLE1 to Regulate mRNA Export and Zebrafish Retinal Development
Wolf, E.J., Miles, A., Lee, E.S., Nabeel-Shah, S., Greenblatt, J.F., Palazzo, A.F., Tropepe, V., Emili, A.
Date: 2020
Source: Cell Reports   31: 107693 (Journal)
Registered Authors: Tropepe, Vincent
Keywords: GLE1, MKRN2, RNA binding proteins, affinity purification mass spectrometry, mRNA export, zebrafish retinogenesis
MeSH Terms:
  • Animals
  • Humans
  • Mass Spectrometry/methods*
  • RNA, Messenger/metabolism*
  • RNA-Binding Proteins/metabolism*
  • Retina/physiopathology*
  • Ribonucleoproteins/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed: 32460013 Full text @ Cell Rep.
The mammalian mRNA nuclear export process is thought to terminate at the cytoplasmic face of the nuclear pore complex through ribonucleoprotein remodeling. We conduct a stringent affinity-purification mass-spectrometry-based screen of the physical interactions of human RNA-binding E3 ubiquitin ligases. The resulting protein-interaction network reveals interactions between the RNA-binding E3 ubiquitin ligase MKRN2 and GLE1, a DEAD-box helicase activator implicated in mRNA export termination. We assess MKRN2 epistasis with GLE1 in a zebrafish model. Morpholino-mediated knockdown or CRISPR/Cas9-based knockout of MKRN2 partially rescue retinal developmental defects seen upon GLE1 depletion, consistent with a functional association between GLE1 and MKRN2. Using ribonomic approaches, we show that MKRN2 binds selectively to the 3' UTR of a diverse subset of mRNAs and that nuclear export of MKRN2-associated mRNAs is enhanced upon knockdown of MKRN2. Taken together, we suggest that MKRN2 interacts with GLE1 to selectively regulate mRNA nuclear export and retinal development.