Experimental evidence for the functional importance and adaptive advantage of A-to-I RNA editing in fungi

Abstract

Adenosine-to-inosine (A-to-I) editing is the most prevalent type of RNA editing in animals, and it occurs in fungi specifically during sexual reproduction. However, it is debatable whether A-to-I RNA editing is adaptive. Deciphering the functional importance of individual editing sites is essential for the mechanistic understanding of the adaptive advantages of RNA editing. Here, by performing gene deletion for 17 genes with conserved missense editing (CME) sites and engineering underedited (ue) and overedited (oe) mutants for 10 CME sites using site-specific mutagenesis at the native locus in Fusarium graminearum , we demonstrated that two CME sites in CME5 and CME11 genes are functionally important for sexual reproduction. Although the overedited mutant was normal in sexual reproduction, the underedited mutant of CME5 had severe defects in ascus and ascospore formation like the deletion mutant, suggesting that the CME site of CME5 is co-opted for sexual development. The preediting residue of Cme5 is evolutionarily conserved across diverse classes of Ascomycota, while the postediting one is rarely hardwired into the genome, implying that editing at this site leads to higher fitness than a genomic A-to-G mutation. More importantly, mutants expressing only the underedited or the overedited allele of CME11 are defective in ascosporogenesis, while those expressing both alleles displayed normal phenotypes, indicating that concurrently expressing edited and unedited versions of Cme11 is more advantageous than either. Our study provides convincing experimental evidence for the long-suspected adaptive advantages of RNA editing in fungi and likely in animals.

Adaptation of A-to-I RNA editing in bacteria, fungi, and animals

“…The editability provides a flexible choice for the organism. Later we will mention that this hypothesis was recently experimentally verified in fungi (Xin et al, 2023).…”

“…The diversifying hypothesis stresses the flexibility (condition-specificity) of RNA editing (Gommans et al, 2009 ). Apart from the well-acknowledged cases of adaptive recoding in insects (Yu et al, 2016 ; Duan et al, 2017 ) and cephalopods (Garrett and Rosenthal, 2012 ; Liscovitch-Brauer et al, 2017 ) that show temporal-spatial regulation, strong evidence was recently found to support the adaptive proteomic diversification of RNA editing in fungi (Xin et al, 2023 ). The pre-edit allele is beneficial in the asexual stage of Fusarium graminearum while the post-edited allele is beneficial in the sexual stage.…”

“…Overall, the editable status is more advantageous than uneditable status (agreeing with the model in Figure 1C ). The relative fitness of two alleles is experimentally measured using mutant strains (Xin et al, 2023 ). This is the first case to prove the advantage of flexible RNA editing over the genomically encoded adenosines or guanosines.…”

Comparative genomic analyses reveal evidence for adaptive A-to-I RNA editing in insect Adar gene

“…For justifying the adaptiveness of individual RNA editing sites, a recent research in fungi has taken significant steps towards addressing ‘how the editable state is better than the uneditable state or hardwired G’ by constructing mutant strains [ 22 ]. In the case of a specific A-to-I RNA editing site in Fusarium graminearum , solid observations proved that the genomically uneditable mutant exhibits higher fitness during the asexual stage, while the genomically fixed-G mutant is fitter during the sexual stage.…”

Expanding the proteome: A-to-I RNA editing provides an adaptive advantage

“…In PNAS, Xin et al. explore the role of A-to-I editing during sexual development of Fusarium graminearum , a filamentous ascomycete ( 10 ). The authors demonstrate that conserved A-to-I editing sites are functionally important during fungal development and provide evidence that A-to-I editing provides an adaptive advantage.…”