Consistent levels of A-to-I RNA editing across individuals in coding sequences and non-conserved Alu repeats

Abstract

Background: Adenosine to inosine (A-to-I) RNA-editing is an essential post-transcriptional mechanism that occurs in numerous sites in the human transcriptome, mainly within Alu repeats. It has been shown to have consistent levels of editing across individuals in a few targets in the human brain and altered in several human pathologies. However, the variability across human individuals of editing levels in other tissues has not been studied so far.

Results: Here, we analyzed 32 skin samples, looking at A-to-I editing level in three genes within coding sequences and in the Alu repeats of six different genes. We observed highly consistent editing levels across different individuals as well as across tissues, not only in coding targets but, surprisingly, also in the non evolutionary conserved Alu repeats.

Conclusions: Our findings suggest that A-to-I RNA-editing of Alu elements is a tightly regulated process and, as such, might have been recruited in the course of primate evolution for post-transcriptional regulatory mechanisms.

Figure 1

Highly regulated A-to-I RNA-editing within coding sequences and Alu repeats in human skin samples. 32 skin samples were tested for editing levels in one site within the coding regions of FLNA, CYFIP2 and BLCAP and within Alu repeat residing in the FYN, KLRD1 and CARD11 genes. A. Consistent editing levels in FLNA, CYFIP2 and BLCAP among different individuals. B. Consistent Alu A-to-I RNA-editing levels in FYN, KLRD1 and CARD11. C. Mean editing level of the six sites ± one standard deviation.

Figure 2

Editing levels of specific sites in a highly-edited region of FYN is consistent among individual human skin tissues. A. Editing levels for sites in a highly-edited region of FYN are presented for 22 skin samples. Site-specific editing levels are consistent among the samples. B. Editing level and variance of the seven tested sites of FYN. Mean editing level of the seven sites ± one standard deviation.

Figure 3

Editing levels in the NARF gene are regulated among different tissues and cell-lines. Data from Lev-Maor et al [34] was analyzed. Editing frequencies of five A-to-I editing sites within the Alu repeat in the 8^th exon of NARF are shown for 13 different tissues and cell-lines.