Accumulation of nuclear ADAR2 regulates adenosine-to-inosine RNA editing during neuronal development

• Adenosine to inosine (A-to-I) RNA editing is important for a functional brain and most known sites of selective RNA editing has been found to diversify the number of protein isoforms involved in neurotransmission. In absence of the active editing enzymes, ADAR1 or ADAR2, mice fail to survive until adulthood. Nuclear A-to-I editing of neuronal transcripts is regulated during brain development with low levels in the embryo and a dramatic increase after birth. Yet, little is known about the mechanisms that regulate editing during development. Here we demonstrate lower levels of ADAR2 in the nucleus of immature neurons than in mature neurons. We show that importin-α4, which increases during neuronal maturation, interacts with ADAR2 and contributes to the editing efficiency by bringing it into the nucleus. Moreover, we detect an increased number of interactions between ADAR2 and the nuclear isomerase Pin1 as neurons mature, which contribute to ADAR2 protein stability. Together, these findings explain how nuclear editing of substrates important for neuronal function can increase as the brain develops.

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)