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NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning
RNA ( IF 4.2 ) Pub Date : 2020-09-22 , DOI: 10.1261/rna.077446.120
Om Singh Rathore 1 , Rui D Silva 1 , Mariana Ascensão-Ferreira 2 , Ricardo Matos 1 , Célia Carvalho 2 , Bruno Marques 1 , Margarida N Tiago 1 , Pedro Prudêncio 1, 2 , Raquel P Andrade 1, 3 , Jean-Yves Roignant 4, 5 , Nuno L Barbosa-Morais 2 , Rui Gonçalo Martinho 1, 2, 6
Affiliation  

The NineTeen Complex (NTC), also known as Pre-mRNA-processing factor 19 (Prp19) complex, regulates distinct spliceosome conformational changes necessary for splicing. During Drosophila 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 Drosophila orthologue of human RNA helicase Aquarius, is rate-limiting for splicing of a subset of small first introns during oogenesis, including the first intron of gurken. Germ line depletion of Salsa and splice site mutations within gurken first intron both impair 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 gurken 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 gurken mRNA. Retention of gurken first intron compromises the function of this gene most likely because it undermines the correct structure and function of the transcript 5'UTR.

中文翻译:


NineTeen 复合体亚基 Salsa 是内含子子集和背腹模式的有效剪接所必需的



NineTeen 复合物 (NTC) 也称为前 mRNA 加工因子 19 (Prp19) 复合物,调节剪接所需的不同剪接体构象变化。在果蝇中囊胚转变期间,剪接对 NTC 亚基 Fandango 的突变特别敏感,这表明发育过程中对 NTC 的需求存在差异。我们发现,NTC 亚基 Salsa(人类 RNA 解旋酶 Aquarius 的果蝇直系同源物)在卵子​​发生过程中对一小部分第一内含子(包括 gurken 的第一内含子)的剪接具有限速作用。由于 Gurken 的异常表达,Salsa 的种系耗竭和 gurken 第一内含子内的剪接位点突变都会损害成年女性的生育能力和卵母细胞背腹模式。支持因果关系的是,Salsa耗尽后观察到的生育力和背腹模式缺陷可以通过表达没有第一个内含子的gurken构建体来抑制。总而言之,我们的结果表明,Salsa 在卵子发生过程中的关键限速功能之一是确保 gurken mRNA 第一个内含子的正确表达和有效剪接。 gurken 第一个内含子的保留很可能会损害该基因的功能,因为它破坏了转录本 5'UTR 的正确结构和功能。
更新日期:2020-09-22
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