PUBLICATION
MKRN2 Physically Interacts with GLE1 to Regulate mRNA Export and Zebrafish Retinal Development
- Authors
- Wolf, E.J., Miles, A., Lee, E.S., Nabeel-Shah, S., Greenblatt, J.F., Palazzo, A.F., Tropepe, V., Emili, A.
- ID
- ZDB-PUB-200528-12
- 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.
Citation
Wolf, E.J., Miles, A., Lee, E.S., Nabeel-Shah, S., Greenblatt, J.F., Palazzo, A.F., Tropepe, V., Emili, A. (2020) MKRN2 Physically Interacts with GLE1 to Regulate mRNA Export and Zebrafish Retinal Development. Cell Reports. 31:107693.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping