[No authors listed]
The maternal contribution of gene products enables embryos to initiate their developmental program in the absence of zygotic gene expression. In Caenorhabditis elegans, maternal CDC-25.1 levels are tightly regulated to promote early cell divisions, while stabilization of this phosphatase by gain-of-function mutations gives rise to intestinal-specific hyperplasia. To identify regulators of CDC-25.1 levels and/or function, we performed a modifier screen of the cdc-25.1(gf)-dependent hyperplasia. One of the isolated suppressor mutants possesses a donor splice site mutation in prp-8, a key splicing factor of the U5-specific snRNP. prp-8(rr40) produces aberrant prp-8 splice variants that generate C-terminal truncations at the expense of wild-type prp-8. Levels of maternal transcripts are reduced, including cdc-25.1, while zygotic transcripts appear unperturbed, suggesting a germ-line-specific role for this splicing factor in regulating the splicing, and consequently, the steady-state levels of maternal transcripts. Using a novel feeding strategy we found that only a subset of splicing factors suppress cdc-25.1(gf), suggesting that they too may play specific roles in germ-line spliceosome function. In humans, mutations in the corresponding hPrp8 C-terminal domain result in retinitis pigmentosa, a retinal-specific disorder. Intriguingly, despite affecting the general splicing apparatus, both human and C. elegans show tissue-specific defects resulting from mutations in this key splicing component. Our findings suggest that in addition to its important regulatory function in the C. elegans germ line, prp-8(rr40) may provide further insight into the etiology of this splicing-associated human disorder.
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snr-7, C50F2.3, prp-31, cdc-25.1, teg-4, cdc-5L, mfap-1, pabp-2, pab-1, prp-17, mag-1, snr-2, prp-21, usp-39, mog-5, snr-3, T13H5.4, stip-1, M28.5, let-858, snrp-200, cacn-1, K09E4.1, mog-4, T08A11.2, rnp-4, R07E5.1, ddx-15, ddx-23, eftu-2, gen-1, snr-5, prp-8, C07A9.2, mog-1, prp-3, snr-6, rsp-3, hrp-1, mtr-4, rack-1, lsm-7, repo-1, F11A10.7, snr-1, uaf-2, M03F8.3, F19F10.9, ruvb-1, K07C5.6, prp-38, plrg-1, F53B7.3, skp-1, snr-4, gut-2, emb-4, T12A2.7, ver-2, lsm-6, prp-19, F53B7.7, sap-49
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