Fmrp Interacts with Adar and Regulates RNA Editing, Synaptic Density and Locomotor Activity in Zebrafish
Fig 5
Transcriptome RNA hyperediting (HE) clusters in zebrafish.
A. Out of the overall 12 possible mismatches between RNA and DNA, there was a cluster enrichment of A-to-G transitions (93%) compared with the other 11 mismatch possibilities (7%). Web-logo diagrams show the abundance of each nucleotide located 1 bp upstream (position -1) and 1 bp downstream (position +1) of every A/G mismatch found in zebrafish. Top panels show the results for both -1 and +1 positions in the zebrafish exons (top right) and whole transcriptome (top left). Consistent with the established motif, ‘G’ is the least represented nucleotide, with 8.4% in whole transcriptome and 11.4% in exons. Bottom panels show the results for both -1 and +1 positions surrounding the 42,500 editing sites comprising the RADAR dataset in humans (bottom left) and mice (bottom right). In position -1, similar to the case of zebrafish, ‘G’ is considerably under-representation with 8.4% and 4.4% in humans and mice, respectively. B. The distribution and number of A-to-I RNA hyperediting (HE) sites. The top chart represents all detected DNA-RNA mismatches. A-to-G mismatches are the majority (93%) of all mismatches. Middle and bottom charts show the genomic location of the detected HE clusters. C. Most of the detected RNA editing sites were found in repeats. Comparison between the distribution of the total and edited repeat families in the zebrafish genome showed an enrichment of the hAT family DNA repeats. While the hAT family occupies only 8% of total repeats in the entire zebrafish genome, it holds 26% of the total cluster containing sequences. D. mfold analysis of RNA secondary structure performed on the two most prominent DNA repeats (ANGEL and TDR19), which are members of the hAT family and account for over 11% of all sites detected. Structure analysis shows a long-stemmed dsRNA structure with palindrome traits that enable Adar binding and, consequently, RNA editing. Color code represents the strength of the nucleotide connection.