CERKL-containing mRNP particles: relevance in retinitis pigmentosa.
28/03/2014, 13h. Salón de Actos del CIPF
Dra. Eva Pérez-Jiménez
Retinitis pigmentosa (RP) is the most common form of hereditary retinal dystrophies with a prevalence of 1:4,000, and is characterized by night blindness and progressive loss of vision due to photoreceptor degeneration. This disease presents an extremely high genetic heterogeneity and to date more that fifty causative genes have been identified. One of these genes is CERKL (CERamide Kinase Like), which was first identified in a Spanish family. Despite its homology with the ceramide kinase CERK, its role in lipid metabolism has not been proven, and its function remains unknown. After investigating its subcellular localization and interaction partners we have demonstrated that CERKL is a main component of compact and untranslated mRNPs and that it can also associate with other RNP complexes such as stress granules, P-bodies and polysomes, depending on its nuclear/cytoplasmic shuttling. We have shown that CERKL interacts with mRNAs and binds to other mRNA-binding proteins like eIF3B, PABP, HSP70 and RPS3. Except for eIF3B, these interactions depended on the integrity of the mRNAs. To confirm the physiological relevance of these findings, we have generated a point mutant found in patients of cone-rod dystrophy (CERKL C125W). Interestingly, the C125W pathological mutant did not enter the nucleus, did not interacted with eIF3B and was absent from those complexes. Compact mRNPs containing CERKL also associate to microtubules and localize in distant compartments in neural differentiated cells. These results support an unexpected role of CERKL in controlling the stability, transport and/or translation of mRNAs. These functions had not been previously reported for any member of the retinal disorders gene family and highlight a new retinal cellular process crucial for a healthy vision.