Research Article: Adenosine to inosine mRNA editing in fungi and how it may relate to fungal pathogenesis

Date Published: September 27, 2018

Publisher: Public Library of Science

Author(s): Ines Teichert, Laurie Read.

http://doi.org/10.1371/journal.ppat.1007231

Abstract

Partial Text

mRNA editing is the occurrence of base substitutions and short insertions or deletions (indels) in an mRNA that could alternatively be directly encoded by the genomic DNA [2]. Typical mRNA editing events are uridine (U) indels as well as cytosine (C)-to-U deamination, reverse U-to-C editing, and adenosine (A) to inosine (I) deamination (Fig 1). Effectively, A-to-I editing generates A-to-guanosine (G) substitutions in coding RNA, because the ribosome interprets I as G during translation.

The occurrence of mRNA editing in fungi was revealed only recently for the basidiomycetes Ganoderma lucidum and Pleurotus ostreatus as well as for the filamentous ascomycetes F. graminearum, F. verticillioides, Neurospora crassa, N. tetrasperma, Pyronema confluens, and Sordaria macrospora [11,12,13,14,15]. In the basidiomycete G. lucidum, editing shows neither a base change nor a tissue preference [14]. However, editing in ascomycetes shows a preference for A-to-I RNA editing specifically during fruiting body formation [11,12,13]. In F. graminearum and N. crassa, editing was detected only in datasets from sexually developing samples, not from asexual spores or vegetative mycelia [11,13]. Interestingly, the ascomycetous yeast Schizosaccharomyces pombe does not show evidence of mRNA editing during meiosis [12]. Thus, RNA editing seems to be restricted to multicellular fungi—specifically A-to-I RNA editing to filamentous ascomycetes that generate fruiting bodies.

Metazoan A-to-I RNA editing of nuclear transcripts is catalyzed by adenosine deaminases acting on RNA (ADARs) [16]. These enzymes deaminate the adenine base to hypoxanthine, resulting in an I instead of an A nucleotide. ADARs contain a deaminase domain and dsRNA-binding domains that bind to double-stranded RNA regions in which the editing sites are located [17]. Besides RNA secondary structure, the base opposite to the target A (preferentially a C) and the flanking nucleotides affect editing efficiency. The human genome encodes five ADARs, two of which show editing activity.

As mentioned above, A-to-I editing of nuclear transcripts leads to proteome diversification. A-to-I editing in humans occurs in a tissue-specific fashion and targets mostly noncoding regions. The few targeted protein-coding transcripts are related to neurological functions [19].

A correlation of RNA editing and pathogenesis has long been known from trypanosomes, e.g., vertebrate parasites like T. brucei and T. cruzi, causing sleeping sickness and Chagas disease in humans, respectively [24]. The first editing event was detected because the trypanosomal mitochondrial coxII gene does contain frame-shifts, implying a faulty gene sequence that needs to be corrected for proper biological function of the encoded protein [25]. The single mitochondrion of T. brucei displays an adaptation to the parasite lifestyle; the procyclic form in the tsetse fly has a standard mitochondrion, whereas the slender bloodstream form (BF) has a tubular mitochondrion with a nonfunctional respiratory chain [26]. Editing activity per se is essential for both the procyclic and the BF type of T. brucei [27]. However, editing of distinct transcripts may be essential just in the BF form [26,28,29].

 

Source:

http://doi.org/10.1371/journal.ppat.1007231