Several Cis-regulatory Elements Control mRNA Stability, Translation Efficiency, and Expression Pattern of Prrxl1 (Paired Related Homeobox Protein-like 1)

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Regadas, I (Author) Other; Matos, MR (Author) Other; Filipe Monteiro (Author) FMUP; Luis Gomez Skarmeta, JL (Author) Other; Lima, D (Author) Other; Bessa, J (Author) Other; Casares, F (Author) Other; reguenga, c (Author) FMUP

Journal

Title: Journal of Biological Chemistry

Vol. 288

Pages: 36285-36301

ISSN: 0021-9258

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-008-K5T

DOI: 10.1074/jbc.m113.491993

Abstract (EN): Background: The mechanisms that control the Prrxl1 expression are poorly understood. Results: Several regulatory elements present in Prrxl1 alternative promoters are functionally characterized, including a binding motif for Phox2b required for Prrxl1 expression in visceral sensory neurons. Conclusion: We define diverse regulatory modules, which control the spatiotemporal expression of Prrxl1 in nociceptive neurons. Significance: A new mechanism involved in the ganglion specific action of Prrxl1 is described. 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 17