Abstract:

microRNAs (miRNAs) are small 22 nucleotide long nucleic acids which are key post-transcriptional regulators of gene expression. It is predicted that miRNAs control up to 1/3 of human coding genes. They control highly regulated processes such as cell differentiation, proliferation and the immune response. Therefore, miRNA processing, maturation and miRNA-mediated gene regulation are very likely highly regulated processes.

While the canonical pathway of miRNA biogenesis is well understood, new auxiliary factors which control miRNA processing are constantly being discovered. Most of the proteins that regulate miRNA maturation are RNA binding proteins.

Here we present a novel function of two RNA binding proteins, p72 and KHSRP in the regulation of the stability of the effector protein of the miRNA pathway. Both p72 and KHSRP regulate the maturation of several miRNAs at the pri-miRNA and pre-miRNA processing steps respectively. We have discovered that the down regulation of these two RNA binding proteins unexpectedly decrease the level of  miRNA effector protein Ago2. We present evidence that this p72 and KHSRP initiate Ago2 degradation post-transcriptionally.