Human TRB3 is upregulated in stressed cells by the induction of translationally efficient mRNA containing a truncated 5'-UTR.

摘要: Tribbles homolog 3 (TRB3) is a pseudokinase that has been implicated in the control of stress response, cell viability and metabolic processes, linked to medical conditions, including insulin resistance, cardiovascular disease diabetes. Therefore, understanding mechanisms regulate TRB3 expression considerable importance. We have previously described existence several human (h) mRNA isoforms differ their 5'-untranslated region (5'-UTR). In this study, we use reverse transcription-quantitative polymerase chain reaction (RT-qPCR) system characterize levels hTRB3 HepG2 hepatoma cells cultured regular medium or exposed arsenite, investigate effect 5'-UTR variants on efficiency translation. The data indicate splice variants, 1A predominant (>80% molecules) both stressed unstressed states, remainder consists mainly 1B4, with 1B1, 1B2 1B3 together forming less than 1% population either condition. addition substantial transcriptional upregulation all exposure arsenite results marked increase proportion variant molecules containing truncated 5'-UTR. shortened proved be translationally more efficient untruncated 5'-UTR, due lack an inhibitory upstream open reading frame (uORF). Thus, increased transcription as well altered usage contributes protein synthesis stressful conditions.