Expression of a Prrxl1 alternative splice variant during the development of the mouse nociceptive system

Abstract

Background Gene expression can be differentially regulated by alternatively spliced transcription factors, providing a mechanism for precise control of diverse morphogenetic events. The paired-type homedomain transcription factor Prrxl1 (formerly known as Drg11) was described as a key regulator of the differentiation of the spinal cord neuronal circuit dedicated to the processing of nociceptive information. Here, we report the characterization of a Prrxl1 alternative splice variant that we termed Prrxl1

Paired related homeobox protein‐like 1 (Prrxl1) controls its own expression by a transcriptional autorepression mechanism

“…As any Prrxl1 co-regulators or co-factors are presently unknown, we cannot distinguish between these two possibilities. We have previously shown that Prrxl1 is the most expressed isoform in developing DRG and dorsal SC [21]. The expression ratio between Prrxl1 and Prrxl1b is kept constant in the DRG, but varies in the dorsal SC during later embryonic and postnatal development [21].…”

“…We have previously shown that Prrxl1 is the most expressed isoform in developing DRG and dorsal SC [21]. The expression ratio between Prrxl1 and Prrxl1b is kept constant in the DRG, but varies in the dorsal SC during later embryonic and postnatal development [21]. Transcriptional autorepression may thus control the expression ratio of Prrxl1 isoforms, being Prrxl1b more effectively repressed than Prrxl1.…”

“…Prrxl1 and Prrxl1b). Both variants retain the N-terminal homeodomain (HD), whereas Prrxl1b lacks the C-terminal Otp-Aristaless-Rax domain (OAR) [21]. Although the regulatory elements controlling Prrxl1 transcription are starting to be identified, the mechanisms underlying spatio-temporal control of Prrxl1 expression are still scarce.…”

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

“…The Prrxl1 mRNA sequence described by these authors contained the start codon in exon 2, whereas exon 1 corresponded to a 5Ј-UTR. More recently, by the use of 5Ј-rapid amplification of cDNA ends assays with mice spinal cord RNA extracts, we described two novel variants of Prrxl1 containing alternative exon 1 that gives rise to distinct 5Ј-UTRs (11). BLAST searches of GenBank TM database led us to identify sequences that correspond to all the three 5Ј-UTRs that contained both the first and the last coding exons of the annotated Prrxl1.…”

“…Recently, a Prrxl1 alternative spliced variant was identified, and multiple variants of exon 1 in both Prrxl1 mRNA isoform sequences were discovered, suggesting the existence of various 5Ј-untranslated regions (5Ј-UTRs) controlled by distinct promoters (11). Modulation of gene expression through alternative promoter usage is now widely accepted following evidence gathered in the past years (12,13).…”