The Argonaute (AGO) proteins form the core components of the RNA induced silencing complex. In RNA interference (RNAi) processes, AGO proteins are guided by bound small RNAs, microRNAs and siRNAs, to (partially) complementary sequences on target RNAs, resulting in target mRNA destabilization or translational repression. In metazoans, post-transcriptional gene silencing by cytoplasmic RNAi processes has been well documented. However, recent reports suggest that components of the RNAi biogenesis pathway, including AGO protein, exhibit some degree of nuclear localization and possibly additional functions beyond canonical miRNA processing. We are combining biochemical and high throughput methods to quantify the levels of nuclear AGO proteins and identify possible transcriptional or posttranscriptional regulatory roles for nuclear AGO ribonucleoproteins.