Several cis-regulatory elements control mRNA stability, translation efficiency, and expression pattern of Prrxl1 (paired related homeobox protein-like 1).
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.
From the Departamento de Biologia Experimental, Faculdade de Medicina do Porto, Universidade do Porto, Porto 4200-319, Portugal.
Isabel
I
Regadas
Mariana Raimundo
MR
Matos
Filipe Almeida
FA
Monteiro
José Luis
JL
Gómez-Skarmeta
Deolinda
D
Lima
José
J
Bessa
Fernando
F
Casares
Carlos
C
Reguenga
D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018507:Gene Expression Regulation, Developmental; D057809:HEK293 Cells; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D016716:PC12 Cells; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D016385:TATA Box; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish
D020121:5' Untranslated Regions; D018398:Homeodomain Proteins; C109220:NBPhox protein; D009419:Nerve Tissue Proteins; C433766:Prrxl1 protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors
5′-UTR; Alternative Promoters; Gene Regulation; Neurodevelopment; Pain; Phox2b; Promoters; Prrxl1; Sensory Neurons; Transcription/Developmental Factors