ADAR2 inhibits ER-targeted mRNA translation via regulating nucleolar assembly of signal recognition particle

Abstract

Adenosine-to-inosine RNA editing is mediated by ADAR family proteins and plays critical roles in regulating gene expression. Unlike other ADAR family members, ADAR2 mostly resides in nucleolus. The exact roles of this peculiar cellular distribution of ADAR2 is still largely unknown. Here, our current study unexpectedly uncovered that nucleoli-localized ADAR2 is involved in negatively regulating ER-targeted mRNA translation, which is mediated by SRP. Importantly, this regulation is not archived through direct binding of mRNA by ADAR2 or dependent on A-to-I editing of 7SL RNA. Further analysis indicated that ADAR2 directly interacts with SRP protein components, especially SRP68, in a RNA-independent manner and probably represses the SRP assembly. Hence, we proved insights into the novel functions of ADAR2 and long-lasting enigma about the peculiar translocation of SRP proteins into nucleoli during SRP biogenesis.