Prpf31, pre-mRNA processing factor 31, is a ubiquitously expressed splicing factor crucial for the assembly of the macromolecular spliceosome. Pre-mRNA splicing is an essential eukaryotic process where intronic sequences are removed before translation into protein [2].

Mutations in Prpf31 cause autosomal dominant retinitis pigmentosa (PRPF31-RP), a form of retinal degeneration leading to progressive visual impairment. Prpf31-RP exhibits incomplete penetrance due to haploinsufficiency [1,2]. In prpf31 knockout zebrafish, the differentiation and viability of retinal progenitor cells (RPCs) are severely perturbed at an early embryonic stage, with significant mitotic arrest and DNA damage. These defects can be rescued by wild-type human PRPF31 but not disease-associated mutants. Prpf31 deletion predominantly causes the skipping of exons with a weak 5' splicing site, and genes for DNA repair and mitotic progression are most enriched among the differentially spliced events [3].

In conclusion, Prpf31 is essential for the survival and differentiation of RPCs during retinal neurogenesis by modulating alternative splicing. The study of Prpf31 in knockout models has provided insights into the pathogenesis of PRPF31-associated retinitis pigmentosa, highlighting its significance in understanding this blinding disease and potentially developing novel therapeutic strategies [1,3].

References:

1. Aweidah, Hamzah, Xi, Zhouhuan, Sahel, José-Alain, Byrne, Leah C. 2023. PRPF31-retinitis pigmentosa: Challenges and opportunities for clinical translation. In Vision research, 213, 108315. doi:10.1016/j.visres.2023.108315. https://pubmed.ncbi.nlm.nih.gov/37714045/

2. Rose, Anna M, Luo, Rong, Radia, Utsav K, Bhattacharya, Shomi S. 2017. Gene of the month: PRPF31. In Journal of clinical pathology, 70, 729-732. doi:10.1136/jclinpath-2016-203971. https://pubmed.ncbi.nlm.nih.gov/28663330/

3. Li, Jingzhen, Liu, Fei, Lv, Yuexia, Tang, Zhaohui, Liu, Mugen. . Prpf31 is essential for the survival and differentiation of retinal progenitor cells by modulating alternative splicing. In Nucleic acids research, 49, 2027-2043. doi:10.1093/nar/gkab003. https://pubmed.ncbi.nlm.nih.gov/33476374/