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Genes 2018, 9(2), 79; https://doi.org/10.3390/genes9020079

Differential Enzymatic Activity of Rat ADAR2 Splicing Variants Is Due to Altered Capability to Interact with RNA in the Deaminase Domain

1
Division of Biology and Genetics-Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
2
Division of Physics, Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 30 November 2017 / Revised: 19 January 2018 / Accepted: 19 January 2018 / Published: 8 February 2018
(This article belongs to the Section Molecular Genetics and Genomics)
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Abstract

In mammals, adenosine (A) to inosine (I) RNA editing is performed by adenosine deaminases acting on RNA (ADAR), ADAR1 and ADAR2 enzymes, encoded by mRNAs that might undergo splicing process. In rat, two splicing events produce several isoforms of ADAR2, called ADAR2a, ADAR2b, ADAR2e, and ADAR2f, but only ADAR2a and ADAR2b are translated into an active protein. In particular, they differ for ten amino acids located in the catalytic domain of ADAR2b. Here, we focused on these two isoforms, analyzing the splicing pattern and their different function during rat neuronal maturation. We found an increase of editing levels in cortical neurons overexpressing ADAR2a compared to those overexpressing ADAR2b. These results indicate ADAR2a isoform as the most active one, as reported for the homologous human short variant. Furthermore, we showed that the differential editing activity is not due to a different dimerization of the two isoforms; it seems to be linked to the ten amino acids loop of ADAR2b that might interfere with RNA binding, occupying the space volume in which the RNA should be present in case of binding. These data might shed light on the complexity of ADAR2 regulations. View Full-Text
Keywords: ADAR2; RNA editing; alternative splicing; neuron ADAR2; RNA editing; alternative splicing; neuron
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Filippini, A.; Bonini, D.; Giacopuzzi, E.; La Via, L.; Gangemi, F.; Colombi, M.; Barbon, A. Differential Enzymatic Activity of Rat ADAR2 Splicing Variants Is Due to Altered Capability to Interact with RNA in the Deaminase Domain. Genes 2018, 9, 79.

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