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Rathore, Om Singh; Silva, Rui D; Ascensão-Ferreira, Mariana; Matos, Ricardo; Carvalho, Célia; Marques, Bruno; Tiago, Margarida N; Prudêncio, Pedro; Andrade, Raquel P; Roignant, Jean-Yves; Barbosa-Morais, Nuno L; Martinho, Rui Gonçalo
RNA, 12/2020, Letnik: 26, Številka: 12Journal Article
The NineTeen Complex (NTC), also known as pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During midblastula transition, splicing is particularly sensitive to mutations in NTC-subunit Fandango, which suggests differential requirements of NTC during development. We show that NTC-subunit Salsa, the ortholog of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of Germline depletion of Salsa and splice site mutations within first intron impair both adult female fertility and oocyte dorsal-ventral patterning, due to an abnormal expression of Gurken. Supporting causality, the fertility and dorsal-ventral patterning defects observed after Salsa depletion could be suppressed by the expression of a construct without its first intron. Altogether, our results suggest that one of the key rate-limiting functions of Salsa during oogenesis is to ensure the correct expression and efficient splicing of the first intron of mRNA. Retention of first intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5'UTR.
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