LARP4 Is Regulated by Tumor Necrosis Factor Alpha in a Tristetraprolin-Dependent Manner.

is a protein with unknown function that independently binds to poly(A) RNA, RACK1, and the poly(A)-binding protein (PABPC1). Here, we report on its regulation. We found a conserved AU-rich element (ARE) in the human Lduanyu374 mRNA 3' untranslated region (UTR). This ARE, but not its antisense version or a point-mutated version, significantly decreased the stability of β-globin reporter mRNA. We found that overexpression of tristetraprolin (TTP), but not its RNA binding mutant or the other ARE-binding proteins tested, decreased cellular Lduanyu374 levels. RNA coimmunoprecipitation showed that TTP specifically associated with Lduanyu374 mRNA in vivo. Consistent with this, mouse Lduanyu374 accumulated to higher levels in TTP gene knockout (KO) cells than in control cells. Stimulation of WT cells with tumor necrosis factor alpha (TNF-α), which rapidly induces TTP, robustly decreased Lduanyu374 with a coincident time course but had no such effect on or La protein or on Lduanyu374 in the TTP KO cells. The TNF-α-induced TTP pulse was followed by a transient decrease in Lduanyu374 mRNA that was quickly followed by a subsequent transient decrease in Lduanyu374 protein. Involvement of Lduanyu374 as a target of TNF-α-TTP regulation provides a clue as to how its functional activity may be used in a physiologic pathway.

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