PUBLICATION
Rbm24 controls poly(A) tail length and translation efficiency of crystallin mRNAs in the lens via cytoplasmic polyadenylation
- Authors
- Shao, M., Lu, T., Zhang, C., Zhang, Y.Z., Kong, S.H., Shi, D.L.
- ID
- ZDB-PUB-200403-71
- Date
- 2020
- Source
- Proceedings of the National Academy of Sciences of the United States of America 117: 7245-7254 (Journal)
- Registered Authors
- Shao, Ming, Shi, De-Li
- Keywords
- Rbm24, cataract, cytoplasmic polyadenylation, lens, zebrafish
- Datasets
- GEO:GSE136006, GEO:GSE136003
- MeSH Terms
-
- Animals
- Cataract/metabolism
- Crystallins/genetics
- Crystallins/metabolism*
- Cytoplasm/metabolism
- Lens, Crystalline/metabolism*
- Models, Animal
- Polyadenylation
- RNA Processing, Post-Transcriptional
- RNA, Messenger/metabolism
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism*
- Transcription Factors/metabolism
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 32170011 Full text @ Proc. Natl. Acad. Sci. USA
Citation
Shao, M., Lu, T., Zhang, C., Zhang, Y.Z., Kong, S.H., Shi, D.L. (2020) Rbm24 controls poly(A) tail length and translation efficiency of crystallin mRNAs in the lens via cytoplasmic polyadenylation. Proceedings of the National Academy of Sciences of the United States of America. 117:7245-7254.
Abstract
Lens transparency is established by abundant accumulation of crystallin proteins and loss of organelles in the fiber cells. It requires an efficient translation of lens messenger RNAs (mRNAs) to overcome the progressively reduced transcriptional activity that results from denucleation. Inappropriate regulation of this process impairs lens differentiation and causes cataract formation. However, the regulatory mechanism promoting protein synthesis from lens-expressed mRNAs remains unclear. Here we show that in zebrafish, the RNA-binding protein Rbm24 is critically required for the accumulation of crystallin proteins and terminal differentiation of lens fiber cells. In the developing lens, Rbm24 binds to a wide spectrum of lens-specific mRNAs through the RNA recognition motif and interacts with cytoplasmic polyadenylation element-binding protein (Cpeb1b) and cytoplasmic poly(A)-binding protein (Pabpc1l) through the C-terminal region. Loss of Rbm24 reduces the stability of a subset of lens mRNAs encoding heat shock proteins and shortens the poly(A) tail length of crystallin mRNAs encoding lens structural components, thereby preventing their translation into functional proteins. This severely impairs lens transparency and results in blindness. Consistent with its highly conserved expression in differentiating lens fiber cells, the findings suggest that vertebrate Rbm24 represents a key regulator of cytoplasmic polyadenylation and plays an essential role in the posttranscriptional control of lens development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping