RNA editing activity is associated with splicing factors in InRNP particles: The nuclear pre-mRNA processing machinery

Multiple members of the ADAR (adenosine deaminases acting on RNA) gene fami ly are involved in A-to-I RNA editing. It has been speculated that they may form a large multicomponent protein complex. Possible candidates for such complexes are large nuclear ribonucleoprotein (InRNP) particles, The InRNP particles consist mainly of four spliceosomal subunits that assemble togeth er with the pre-mRNA to form a large particle and thus are viewed as the na turally assembled pre-mRNA processing machinery. Here we investigated the p resence of ADARs in InRNP particles by Western blot analysis using anti-ADA R antibodies and by indirect immunoprecipitation. Both ADAR1 and ADAR2 were found associated with the spliceosomal components Sm and SR proteins withi n the InRNP particles. The two ADARs, associated with InRNP particles, were enzymatically active in site-selective A-to-I RNA editing. We demonstrate the association of ADAR RNA editing enzymes with physiological supramolecul ar complexes, the InRNP particles.