NineTeen Complex-subunit Salsa is required for efficient splicing of a subset of introns and dorsal-ventral patterning

Autor: Nuno L. Barbosa-Morais, Rui D. Silva, Ricardo Matos, Pedro Prudêncio, Om Singh Rathore, Margarida N. Tiago, Jean-Yves Roignant, Mariana Ascensão-Ferreira, Rui Gonçalo Martinho, Célia Carvalho, Bruno Marques, Raquel P. Andrade
Přispěvatelé: Repositório da Universidade de Lisboa
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
RNA
RNA, vol. 26, no. 12, pp. 1935-1956
Popis: © 2020 Rathore et al. This article is distributed exclusively by the RNASociety for the first 12 months after the full-issue publication date (see http://rnajournal.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
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 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 gurken Germline depletion of Salsa and splice site mutations within gurken 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 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.
The Microscopy Unit was partially supported by Portuguese national funding (FCT: PPBI-POCI-01-0145-FEDER-022122). This work was developed with the support of the research infrastructure Congento (project LISBOA-01-0145-FEDER-022170). R.G.M. is supported by Portuguese national funding through Fundação para a Ciência e a Tecnologia (FCT grant refs. PTDC/BEX-BID/0395/2014, PTDC/BIA-BID/28441/2017, and UID/BIM/04773/2013 CBMR 1334). Nuno L. Barbosa-Morais is supported by European Molecular Biology Organization (EMBO) Installation Grant (3057), Investigador FCT Starting Grant (IF/00595/2014), UID/BIM/50005/2019, the project funded by Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado and iMM Lisboa start-up funds. O.S.R. and B.M. were supported by Portuguese national funding through Fundação para a Ciência e a Tecnologia, respectively, PD/BD/52428/2013 and PD/BD/128342/2017, within the scope of the ProRegeM PhD program (ref. PD/00117/2012, CRM:0027030). O.S.R. was also supported by a Federation of European Biochemical societies (FEBS) short-term fellowship. M.A.-F. is supported by Fundação para a Ciência e Tecnologia (FCT) PhD fellowship (PD/BD/128283/2017) and Fundação AstraZeneca. R.D.S. is supported by Portuguese national funding through Fundação para a Ciência e a Tecnologia, ref. DL 57/2016/CP1361/CT0019.
Databáze: OpenAIRE
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