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Publication : Several cis-regulatory elements control mRNA stability, translation efficiency, and expression pattern of Prrxl1 (paired related homeobox protein-like 1).

First Author  Regadas I Year  2013
Journal  J Biol Chem Volume  288
Issue  51 Pages  36285-301
PubMed ID  24214975 Mgi Jnum  J:207190
Mgi Id  MGI:5554643 Doi  10.1074/jbc.M113.491993
Citation  Regadas I, et al. (2013) Several cis-regulatory elements control mRNA stability, translation efficiency, and expression pattern of Prrxl1 (paired related homeobox protein-like 1). J Biol Chem 288(51):36285-301
abstractText  The homeodomain transcription factor Prrxl1/DRG11 has emerged as a crucial molecule in the establishment of the pain circuitry, in particular spinal cord targeting of dorsal root ganglia (DRG) axons and differentiation of nociceptive glutamatergic spinal cord neurons. Despite Prrxl1 importance in the establishment of the DRG-spinal nociceptive circuit, the molecular mechanisms that regulate its expression along development remain largely unknown. Here, we show that Prrxl1 transcription is regulated by three alternative promoters (named P1, P2, and P3), which control the expression of three distinct Prrxl1 5'-UTR variants, named 5'-UTR-A, 5'-UTR-B, and 5'-UTR-C. These 5'-UTR sequences confer distinct mRNA stability and translation efficiency to the Prrxl1 transcript. The most conserved promoter (P3) contains a TATA-box and displays in vivo enhancer activity in a pattern that overlaps with the zebrafish Prrxl1 homologue, drgx. Regulatory modules present in this sequence were identified and characterized, including a binding site for Phox2b. Concomitantly, we demonstrate that zebrafish Phox2b is required for the expression of drgx in the facial, glossopharyngeal, and vagal cranial ganglia.
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