Figure 3.

Alternative splicing of CRFR-1 and CRFR-2 pre-mRNA leads to production of several isoforms of the receptors. A, Human CRFR-1 protein sequence is coded by 14 exons that could be subjected to alternative splicing. Expression of at least 12 isoforms was detected so far in humans and rodents (49, 80, 111). Protein coding exons are shown in violet. Alternative splicing results occasionally in the introduction of termination codon, and some exons no longer code protein (white squares). B, Human CRFR-2 gene contains 15 exons with 3 alternative transcription start codons located in different exons. Three main isoforms were described (CRFR-1α, β, and γ), and at least 7 others were detected, including “headless” isoform. Interestingly, some isoforms (CRFR-2α3, CRFR-2α4, CRFR-2α5) show the retention of intronic segment in the coding sequence. Isoforms CRFR-2α2 and CRFR-2β2 have deletion of 3 nucleotides coding glutamine: CRFR-2β (desQ126) and CRFR-2β-2 (desQ126) (227). Positions of exon 1–14 for CRFR-1 and 1–15 for CRFR-2 are marked on the top of each panel. 7-TM domains are shown as dashed-line squares numbered I–VII (49, 80, 81).