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

Author:

Rathore Om Singh,Silva Rui D.ORCID,Ascensão-Ferreira Mariana,Matos Ricardo,Carvalho Célia,Marques Bruno,Tiago Margarida N.,Prudêncio Pedro,Andrade Raquel P.,Roignant Jean-YvesORCID,Barbosa-Morais Nuno L.ORCID,Martinho Rui Gonçalo

Abstract

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.

Funder

Harvard Medical School

Portuguese national funding

research infrastructure Congento

Portuguese national funding through Fundação para a Ciência e a Tecnologia

EMBO) Installation Grant

Investigador FCT Starting Grant

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

ProRegeM PhD program

Federation of European Biochemical societies (FEBS) short-term fellowship

Fundação para a Ciência e Tecnologia (FCT) PhD fellowship

Fundação AstraZeneca

Publisher

Cold Spring Harbor Laboratory

Subject

Molecular Biology

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