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Free keywords:
AU-RICH ELEMENT; MESSENGER-RNA TURNOVER; ZINC-FINGER PROTEINS;
BINDING-PROTEIN; GENE-EXPRESSION; HNRNP D; HUR; DEGRADATION; DECAY;
TRISTETRAPROLIN
Abstract:
mRNA decay mediated by the AU-rich elements (AREs) is one of the most studied post-transcriptional mechanisms and is modulated by ARE-binding proteins (ARE-BPs). To understand the regulation of K homology splicing regulatory protein (KSRP), a decay-promoting ARE-BP, we purified KSRP protein complexes and identified an RNA helicase, DDX1. We showed that down-regulation of DDX1 expression elevated cytoplasmic levels of KSRP and facilitated ARE-mediated mRNA decay. Association of KSRP with 14-3-3 proteins, that are predominately located in the cytoplasm, increased upon reduction of DDX1. We also demonstrated that KSRP associated with DDX1 or 14-3-3, but not both. These observations indicate that subcellular localization of KSRP is regulated by competing interactions with DDX1 or 14-3-3.
