Location: Genetics and Animal BreedingTitle: Characterization of A-to-I editing events in fetal pig tissues
|CORBETT, RYAN - MICHIGAN STATE UNIVERSITY|
|FUNKHOUSER, SCOTT - MICHIGAN STATE UNIVERSITY|
|Nonneman, Danny - Dan|
|Smith, Timothy - Tim|
|ERNST, CATHY - MICHIGAN STATE UNIVERSITY|
Submitted to: International Society for Animal Genetics (ISAG)
Publication Type: Abstract Only
Publication Acceptance Date: 3/4/2019
Publication Date: 7/12/2019
Citation: Corbett, R.J., Funkhouser, S.A., Nonneman, D.J., Smith, T.P.L., Ernst, C.W. 2019. Characterization of A-to-I editing events in fetal pig tissues [abstract]. In Proceedings: 37th International Society for Animal Genetics (ISAG). 7-12 July 2019, Lleida, Spain. pg. 24. Abstract OP86.
Technical Abstract: RNA editing results in alterations to RNA molecules, producing transcript sequences that are inherently different from the parent DNA molecule. Adenosine-to-Inosine (A-to-I) editing is widespread in metazoans, and is carried out by adenosine deaminase acting on RNA (ADAR) enzymes. The extent to which A-to-I editing influences transcript diversity in the pig has been evaluated; however current studies have been conducted primarily in adult tissues, limiting understanding of how editing processes or patterns change during pig development. The objective of this study was to assess A-to-I editing dynamics in 4 pig fetal tissues (whole brain, liver, skeletal muscle, and placenta) at 30 and 70 d gestation (dg). RNA-sequencing data from each tissue as well as whole-genome sequencing data for a single 70dg White-Composite x Meishan pig were used to identify A-to-G DNA-to-RNA mismatches—indicative of putative A-to-I edits—using the editTools R package. High-confidence sites were subsequently scanned in RNA-seq data from tissues of 3 additional pigs (1 70dg, 2 30dg) to identify conserved mismatch sites. We identified a total of 618 putative shared A-to-I editing sites, with 249, 60, 110, 199 sites identified in brain, liver, muscle, and placenta, respectively. We observed a significant increase in mean editing level across sites in brain (p = 0.011), and a significant decrease in mean editing level of sites in muscle (p = 0.045) from 30dg to 70dg. Consistent with changes in mean editing level, brain tissue exhibited an increase in ADAR2 transcript abundance at 70dg (log2FC = 0.82, P = 0.06), while muscle exhibited a decrease in ADAR1 abundance (log2FC = -0.377, P = 0.03). We identified 22 differentially edited sites between stages, the majority of which were brain-specific and exhibited increased editing at 70dg, and resulted in variants in intronic, 3’ UTR, and coding sequences. Our results suggest dynamic global and site-specific editing patterns in tissues with differential ADAR expression throughout development. Future work will assess editing patterns at high-confidence sites identified in adult pig tissues in the fetal transcriptome.