Faithful mRNA splicing depends on the Prp19 complex subunit faint sausage and is required for tracheal branching morphogenesis in Drosophila

Development. 2017 Feb 15;144(4):657-663. doi: 10.1242/dev.144535. Epub 2017 Jan 13.

Abstract

Morphogenesis requires the dynamic regulation of gene expression, including transcription, mRNA maturation and translation. Dysfunction of the general mRNA splicing machinery can cause surprisingly specific cellular phenotypes, but the basis for these effects is not clear. Here, we show that the Drosophila faint sausage (fas) locus, which is implicated in epithelial morphogenesis and has previously been reported to encode a secreted immunoglobulin domain protein, in fact encodes a subunit of the spliceosome-activating Prp19 complex, which is essential for efficient pre-mRNA splicing. Loss of zygotic fas function globally impairs the efficiency of splicing, and is associated with widespread retention of introns in mRNAs and dramatic changes in gene expression. Surprisingly, despite these general effects, zygotic fas mutants show specific defects in tracheal cell migration during mid-embryogenesis when maternally supplied splicing factors have declined. We propose that tracheal branching, which relies on dynamic changes in gene expression, is particularly sensitive for efficient spliceosome function. Our results reveal an entry point to study requirements of the splicing machinery during organogenesis and provide a better understanding of disease phenotypes associated with mutations in general splicing factors.

Keywords: Branching morphogenesis; Drosophila melanogaster; Faint sausage; Fandango; Spliceosome; Tracheal system; mRNA splicing.

MeSH terms

  • Alleles
  • Animals
  • Cell Movement
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism
  • Embryonic Development
  • Female
  • Gene Expression Regulation, Developmental
  • Immunoglobulins / metabolism
  • Introns
  • Male
  • Morphogenesis
  • Mutation
  • Neuropeptides / metabolism*
  • RNA Precursors / genetics
  • RNA Splicing Factors / metabolism*
  • RNA Splicing Factors / physiology
  • RNA Splicing*
  • RNA, Messenger / metabolism
  • Spliceosomes / metabolism
  • Trachea / embryology*
  • Trachea / metabolism

Substances

  • CG17716 protein, Drosophila
  • Drosophila Proteins
  • Immunoglobulins
  • Neuropeptides
  • RNA Precursors
  • RNA Splicing Factors
  • RNA, Messenger
  • Prp19 protein, Drosophila