Phosphorylation of the human microRNA-generating complex mediates MAPK/Erk signaling.

ABSTRACT: MicroRNAs (miRNAs) govern an expanding number of biological and disease processes. Understanding the mechanisms by which the miRNA pathway is regulated, therefore, represents an important area of investigation. We determined that the human miRNA-generating complex is comprised of Dicer and phospho-TRBP isoforms. Phosphorylation of TRBP is mediated by the mitogen-activated protein kinase (MAPK) Erk. Expression of phospho-mimic TRBP and TRBP phosphorylation enhanced miRNA production by increasing stability of the miRNA-generating complex. Mitogenic signaling in response to serum and the tumor promoter PMA was dependent on TRBP phosphorylation. These effects were accompanied by a coordinated increase in levels of growth-promoting miRNA and reduced expression of let-7 tumor suppressor miRNA. C

SUBMITTER: Paroo Z 

PROVIDER: S-EPMC2760040 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature