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Abstract
Post-transcriptional RNA editing may regulate transcript expression and diversity in cells, with potential impacts on various aspects of physiology and environmental adaptation. A small number of recent genome-wide studies in Drosophila, mouse, and human have shown that RNA editing can be genetically modulated, highlighting loci that quantitatively impact editing of transcripts. The potential gene expression and physiological consequences of these RNA-editing quantitative trait loci (edQTL), however, are almost entirely unknown. Here, we present analyses of RNA editing in a large domestic mammal (Bos taurus), where we use whole-genome and high-depth RNA sequencing to discover, characterize, and conduct genetic mapping studies of novel transcript edits. Using a discovery population of nine deeply sequenced cows, we identify 2413 edit sites in the mammary transcriptome, the majority of which are adenosine to inosine edits (98.6%). Most sites are predicted to reside in double-stranded secondary structures (85.1%), and quantification of the rates of editing in an additional 355 cows reveals editing is negatively correlated with gene expression in the majority of cases. Genetic analyses of RNA editing and gene expression highlight 152 cis-regulated edQTL, of which 15 appear to cosegregate with expression QTL effects. Trait association analyses in a separate population of 9989 lactating cows also shows 12 of the cis-edQTL coincide with at least one cosegregating lactation QTL. Together, these results enhance our understanding of RNA-editing dynamics in mammals, and suggest mechanistic links by which loci may impact phenotype through RNA editing mediated processes.
Highlights
The process of gene expression involves transcribing the information stored in DNA into messenger RNA
Editing sites in lactating mammary tissue have not been previously reported in bovine studies, though of the recent bovine studies examining editing in other tissues, our data set includes 121 of the 1600 sites reported by Bakhtiarizadeh et al (2018), and 92 of the 671 sites reported by Chen et al (2016)
We report the discovery of 2413 RNA editing sites in the bovine mammary transcriptome, and subsequently explore the genomic context and properties of these sites
Summary
The process of gene expression involves transcribing the information stored in DNA into messenger RNA (mRNA). Depending on the location of edits within the pre-mRNA transcript, other potential consequences of RNA editing can include changes to the coding sequence, the creation or destruction of splice sites (Nishikura 2010), triggering of nuclear retention mechanisms of edited transcripts (Zhang and Carmichael 2001; Prasanth et al 2005), or the creation or destruction of microRNA (miRNA) binding sites within the 3′-UTR (Liang and Landweber 2007; Wang et al 2013) These changes in turn can affect gene expression, either as part of normal regulation (Goldstein et al 2017), in a pathogenic context such as cancer (Zhang et al 2016; Baysal et al 2017), or as a mechanism to regulate alternative splicing (Solomon et al 2013)
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