Rbm24 Controls Poly(A) Tail Length And Translation Efficiency Of Crystallin MRNAs In The Lens Via Cytoplasmic Polyadenylation

During development of the vertebrate eye,transparent lens structure with refraction power forms to ensure the acquisition of images from the surrounding environment.Lens transparency depends on the degradation of nuclei as well as other organelles in the differentiating lens fiber cells,accompanied by production of large amounts of crystallin proteins to endow the refraction power.Improper regulation of this process may lead to opaque lens,or cataract,which is the leading cause of human blindness.As the denucleation process impedes prolonged transcription of lens specific mRNAs,the massive accumulation of lens specific proteins can only be achieved by highly efficient translation to overcome the progressively compromised lens mRNA production.In this scenario,posttranscriptional mechanisms controlling efficient mRNA translation become especially important,but are not yet clear at the momentHere 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(Cpeblb)and cytoplasmic poly(A)-binding protein(Pabpcll)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.