Several Cis-regulatory Elements Control mRNA Stability, Translation Efficiency, and Expression Pattern of Prrxl1 (Paired Related Homeobox Protein-like 1)
- Authors
- Regadas, I., Matos, M.R., Monteiro, F.A., Gomez-Skarmeta, J.L., Lima, D., Bessa, J., Casares, F., and Reguenga, C.
- ID
- ZDB-PUB-131218-22
- Date
- 2013
- Source
- The Journal of biological chemistry 288(51): 36285-301 (Journal)
- Registered Authors
- Bessa, Jose, Casares, Fernando, Gómez-Skarmeta, José Luis
- Keywords
- 5 UTR, Gene regulation, Neurodevelopment, Pain, Phox2b, Promoters, Prrxl1, Transcription/developmental factors, alternative promoters, sensory neurons
- MeSH Terms
-
- 5' Untranslated Regions*
- Animals
- Base Sequence
- Binding Sites
- Gene Expression Regulation, Developmental
- HEK293 Cells
- HeLa Cells
- Homeodomain Proteins/genetics*
- Homeodomain Proteins/metabolism
- Humans
- Mice
- Molecular Sequence Data
- Nerve Tissue Proteins/genetics*
- Nerve Tissue Proteins/metabolism
- Neurons/metabolism
- PC12 Cells
- Protein Biosynthesis
- RNA Stability*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism*
- Rats
- TATA Box
- Transcription Factors/genetics*
- Transcription Factors/metabolism
- Transcription, Genetic*
- Zebrafish
- PubMed
- 24214975 Full text @ J. Biol. Chem.
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 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 5UTR variants, named 5UTR-A, 5UTR-B and 5UTR-C. These 5UTR 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.