RNA结合蛋白对调节基因表达和组织特异性可变剪切有至关重要的作用。在脊椎动物眼睛晶状体的分化过程中细胞器降解受阻和纤维化异常是导致先天性白内障的重要原因。Rbm24基因在脊椎动物中高度保守地表达在晶状体中，但它如何调节晶状体的分化还是一个完全空白的研究领域。我们发现在斑马鱼中敲除Rbm24a后使晶状体细胞器降解受阻，作为分子伴侣的晶体基因表达显著下调，导致晶状体透明度异常，说明它对晶状体分化有重要作用。本项目将基于这些发现深入阐明Rbm24a调节晶状体分化的分子机制，开展原创性的工作。进一步的研究目标旨在鉴定与Rbm24a互作的蛋白质以及它们共同调控的靶基因，并在全基因组水平上揭示依赖于Rbm24a的晶状体组织特异性可变剪切事件，明确Rbm24a的作用方式和调节晶状体分化的基因网络。本研究对充分认识晶状体分化和白内障形成的分子机制有重要的理论意义，对预防和治疗眼科疾病有潜在的应用前景。

RNA-binding proteins play important roles in regulating gene expression and tissue-specific alternative splicing events, and are critically involved in organ development and homeostasis. However, only a few tissue-specific splicing factors have been identified at present. Vertebrate lens differentiation requires the degradation of all cytoplasmic organelles (nucleus, Golgi apparatus, endoplasmic reticulum, mitochondria, etc), and the expression of different crystallin proteins, to establish and maintain lens transparency. Genetic mutations of lens-specific regulatory and structural genes lead to defects in lens differentiation and are responsible for congenital and age-related cataracts. The gene encoding a RNA-binding protein, Rbm24, is particularly conserved and is strongly expressed in the lenses of all vertebrates, but its precise function in lens differentiation remains largely unexplored. We found that knockout of Rbm24a in zebrafish markedly delayed the degradation of lens cytoplasmic organelles and specifically down-regulated the expression level of αA-crystallin gene, but not ßB-crystallin and γ-crystallin genes. Cataract formation was observed at 3-day of development. These observations suggest an important role for Rbm24a in the process of lens differentiation. Based on these results, we project to thoroughly analyse the implication and mechanism of Rbm24a in lens differentiation. Since Rbm24 contains only one RNA recognition motif and often operates with other proteins to perform tissue-specific function, we will first identify the interaction partners of Rbm24a in the lenses and determine the target genes regulated by Rbm24a in cooperation with its protein partners. To provide further insight into the tissue-specific function of Rbm24a and the gene regulatory network operating during lens differentiation, we also plan to perform genome-wide identification of Rbm24a-dependent lens tissue-specific alternative splicing events. This work should help to better understand the molecular mechanism underlying lens differentiation and cataract formation. It should also provide insight into the molecular pathways involved in human ocular pathologies.