Conservation of A-to-I RNA editing in bowhead whale and pig.

Knud Larsen,Mads Peter Heide-Jørgensen,Alexander F Palazzo

doi:10.1371/journal.pone.0260081

Knud Larsen, Mads Peter Heide-Jørgensen + Show 1 more

Open Access

https://doi.org/10.1371/journal.pone.0260081

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Journal: PloS one	Publication Date: Dec 9, 2021
Citations: 2	License type: CC BY 4.0

Affiliation: Aarhus University, Grønlands Naturinstitut

Abstract

RNA editing is a post-transcriptional process in which nucleotide changes are introduced into an RNA sequence, many of which can contribute to proteomic sequence variation. The most common type of RNA editing, contributing to nearly 99% of all editing events in RNA, is A-to-I (adenosine-to-inosine) editing mediated by double-stranded RNA-specific adenosine deaminase (ADAR) enzymes. A-to-I editing at ‘recoding’ sites results in non-synonymous substitutions in protein-coding sequences. Here, we present studies of the conservation of A-to-I editing in selected mRNAs between pigs, bowhead whales, humans and two shark species. All examined mRNAs–NEIL1, COG3, GRIA2, FLNA, FLNB, IGFBP7, AZIN1, BLCAP, GLI1, SON, HTR2C and ADAR2 –showed conservation of A-to-I editing of recoding sites. In addition, novel editing sites were identified in NEIL1 and GLI1 in bowhead whales. The A-to-I editing site of human NEIL1 in position 242 was conserved in the bowhead and porcine homologues. A novel editing site was discovered in Tyr244. Differential editing was detected at the two adenosines in the NEIL1 242 codon in both pig and bowhead NEIL1 mRNAs in various tissues and organs. No conservation of editing of KCNB1 and EEF1A mRNAs was seen in bowhead whales. In silico analyses revealed conservation of five adenosines in ADAR2, some of which are subject to A-to-I editing in bowheads and pigs, and conservation of a regulatory sequence in GRIA2 mRNA that is responsible for recognition of the ADAR editing enzyme.

Highlights

RNA editing is a molecular process in which nucleotide changes are introduced into an RNA sequence after transcription
Using RT-polymerase chain reaction (PCR) and RNA purified from organs and tissues of pigs, bowhead whales, spiny dogfish (Squalus acanthias) and Greenland sharks (Somniosus microcephalus), we amplified short NEIL1 cDNA fragments containing the recoding site
The results from Sanger sequencing of the NEIL1 amplicons revealed conservation of A-to-I editing in K242 of the second and third adenosine in pig NEIL1 compared with the human NEIL1 transcript (Fig 1B and 1C and Table 1) and conservation of editing of the second adenosine in the bowhead NEIL1 pre-mRNA (Fig 1D–1F)

Summary

Introduction

RNA editing is a molecular process in which nucleotide changes are introduced into an RNA sequence after transcription. Numerous editing events contribute to proteomic sequence variation [1, 2]. Over 100 different types of RNA editing have been found and more than 340 functionally characterized proteins involved in RNA modification identified [6]. Most editing occurs within repetitive elements such as Alu elements and SINEs. RNA editing is found in tRNA, rRNA, mRNA, and miRNA molecules from both eukaryotes and prokaryotes [7]. RNA editing is widely distributed in the cell and occurs in the nucleus, and within mitochondria [8].

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