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Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system.

ABSTRACT: Adenosine to inosine RNA editing in protein-coding messenger RNAs (mRNAs) potentially leads to changes in the amino acid composition of the encoded proteins. The mRNAs encoding the ubiquitously expressed actin-crosslinking proteins Filamin A and Filamin B undergo RNA editing leading to a highly conserved glutamine to arginine exchange at the identical position in either protein. Here, by targeted amplicon sequencing we analysed the RNA editing of Filamin B across several mouse tissues during post-natal development. We find highest filamin B editing levels in skeletal muscles, cartilage and bones, tissues where Filamin B function seems most important. Through the analysis of Filamin B editing in mice deficient in either ADAR1 or 2, we identified ADAR2 as the enzyme responsible for Filamin B RNA editing. We show that in neuronal tissues Filamin B editing drops in spliced transcripts indicating regulated maturation of edited transcripts. We show further that the variability of Filamin B editing across several organs correlates with its mRNA expression.

SUBMITTER: Czermak P

PROVIDER: S-EPMC6161736 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system.

Czermak Philipp P Czermak Philipp P Amman Fabian F Jantsch Michael F MF Cimatti Laura L

RNA biology 20180731 7

Adenosine to inosine RNA editing in protein-coding messenger RNAs (mRNAs) potentially leads to changes in the amino acid composition of the encoded proteins. The mRNAs encoding the ubiquitously expressed actin-crosslinking proteins Filamin A and Filamin B undergo RNA editing leading to a highly conserved glutamine to arginine exchange at the identical position in either protein. Here, by targeted amplicon sequencing we analysed the RNA editing of Filamin B across several mouse tissues during pos ...[more]

PMID: 30064337

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Project description:BackgroundThe widely observed RNA-DNA differences (RDDs) have been found to be due to nucleotide alteration by RNA editing. Canonical RNA editing (i.e., A-to-I and C-to-U editing) mediated by the adenosine deaminases acting on RNA (ADAR) family and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC) family during the transcriptional process is considered common and essential for the development of an individual. To date, an increasing number of RNA editing sites have been reported in human, rodents, and some farm animals; however, genome-wide detection of RNA editing events in sheep has not been reported. The aim of this study was to identify RNA editing events in sheep by comparing the RNA-seq and DNA-seq data from three biological replicates of the kidney and spleen tissues.ResultsA total of 607 and 994 common edited sites within the three biological replicates were identified in the ovine kidney and spleen, respectively. Many of the RDDs were specific to an individual. The RNA editing-related genes identified in the present study might be evolved for specific biological functions in sheep, such as structural constituent of the cytoskeleton and microtubule-based processes. Furthermore, the edited sites found in the ovine BLCAP and NEIL1 genes are in line with those in previous reports on the porcine and human homologs, suggesting the existence of evolutionarily conserved RNA editing sites and they may play an important role in the structure and function of genes.ConclusionsOur study is the first to investigate RNA editing events in sheep. We screened out 607 and 994 RNA editing sites in three biological replicates of the ovine kidney and spleen and annotated 164 and 247 genes in the kidney and spleen, respectively. The gene function and conservation analysis of these RNA editing-related genes suggest that RNA editing is associated with important gene function in sheep. The putative functionally important RNA editing sites reported in the present study will help future studies on the relationship between these edited sites and the genetic traits in sheep.

Dataset Information

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system.

Publications

Organ-wide profiling in mouse reveals high editing levels of Filamin B mRNA in the musculoskeletal system.

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