Functions and mechanisms of A-to-I RNA editing in filamentous ascomycetes

Abstract

Although lack of ADAR (adenosine deaminase acting on RNA) orthologs, genome-wide A-to-I editing occurs specifically during sexual reproduction in a number of filamentous ascomycetes, including Fusarium graminearum and Neurospora crassa. Unlike ADAR-mediated editing in animals, fungal A-to-I editing has a strong preference for hairpin loops and U at -1 position, which leads to frequent editing of UAG and UAA stop codons. Majority of RNA editing events in fungi are in the coding region and cause amino acid changes. Some of these editing events have been experimentally characterized for providing heterozygote and adaptive advantages in F. graminearum. Recent studies showed that FgTad2 and FgTad3, 2 ADAT (adenosine deaminase acting on tRNA) enzymes that normally catalyze the editing of A34 in the anticodon of tRNA during vegetative growth mediate A-to-I mRNA editing during sexual reproduction. Stage specificity of RNA editing is conferred by stage-specific expression of short transcript isoforms of FgTAD2 and FgTAD3 as well as cofactors such as AME1 and FIP5 that facilitate the editing of mRNA in perithecia. Taken together, fungal A-to-I RNA editing during sexual reproduction is catalyzed by ADATs and it has the same sequence and structural preferences with editing of A34 in tRNA.

Fig 1. Sequence preference of mRNA editing and stop codon editing in F. graminearum editing in fungi.

(A) A-to-I mRNA strongly favors U at the −1 position. (B) A-to-I editing of UAG leads to premature stop codon correction (PSC) and stop-loss editing. Editing of UAA to UGA retains the stop codon. PS, CS, and IS represent premature, canonical, and in-frame stop codons, respectively. (C) PSC, stop-loss, and stop-retaining editing events in F. graminearum.

Fig 2. A model for editing of A34 in tRNA and A-to-I mRNA editing by FgTad2 and FgTad3.

In vegetative hyphae, the FgTad2L and FgTad3 heterodimer functions as regular ADAT to edit A34 in the anticodon loop of tRNA. During sexual reproduction, the expression of short isoforms and stage-specific cofactors, including Ame1 and Fip5, enable the editing of adenosines in the hair loops (favored) and stems (dsRNA regions) of mRNA by the FgTad2S-FgTad3-cofactor protein complex.