a Center of Anatomy and Cell Biology, Division of Cell Biology , Medical University of Vienna , Vienna , Austria.
b Institute of Theoretical Biochemistry , University of Vienna , Vienna , Austria.
RNA Biol. 2018;15(7):877-885. doi: 10.1080/15476286.2018.1480252. Epub 2018 Jul 31.
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.
腺嘌呤核苷向肌苷核苷的 RNA 编辑可能导致编码蛋白的氨基酸组成发生变化。广泛表达的肌动蛋白交联蛋白 Filamin A 和 Filamin B 的编码 mRNA 经历 RNA 编辑，导致在任一蛋白的相同位置上高度保守的谷氨酰胺到精氨酸的替换。在这里，我们通过靶向扩增子测序分析了 Filamin B 在出生后发育过程中几种小鼠组织中的 RNA 编辑。我们发现骨骼肌、软骨和骨骼中的 Filamin B 编辑水平最高，这些组织中 Filamin B 的功能似乎最为重要。通过分析 ADAR1 或 2 缺失的小鼠中的 Filamin B 编辑，我们确定 ADAR2 是负责 Filamin B RNA 编辑的酶。我们表明，在神经元组织中，Filamin B 编辑在剪接转录本中减少，表明编辑转录本的成熟受到调控。我们进一步表明，几个器官中 Filamin B 编辑的可变性与其 mRNA 表达相关。
