Abstract
Human adrenal steroid 21-hydroxylase (P450c21) is encoded by the CYP21A1 (21B) gene located in the class III region of the HLA locus. A tandemly duplicated gene designated CYP21A1P (21A), which lies 30 kilobases upstream, contains several point mutations and an 8-base pair deletion so that it cannot encode P450c21 protein; as a result, it is generally considered to be a pseudogene. We previously showed that two additional genes, XA and XB, lie on the opposite strand of DNA overlapping the 3'-ends of the 21A and 21B genes. We have now identified a third pair of duplicated overlapping genes in this locus, termed YA and YB, whose transcriptional orientation is the same as 21A and 21B and opposite to XA and XB. YA transcripts use the 21A promoter, have 5'-ends that are similar to 21B mRNA, and have approximately 10-20% of the abundance of 21B transcripts, but have unique 3'-ends. The YA gene encodes a 7.5-kilobase RNA that overlaps XA completely and a 3.0-kilobase RNA that excludes most of XA. The YB gene appears to be similar in size and organization to YA. The YA and YB genes extend beyond the limit of the duplication in this locus; hence, their cDNAs are distinguishable by differences in their 3'-sequences. YA and YB transcripts are expressed only in the fetal and adult adrenal glands, but their cDNAs do not contain a long open reading frame. Although the function of these genes is not yet clear, the complex genetic organization of three overlapping genes (21/X/Y) appears to be unique among higher eukaryotes. As YA transcription is initiated by the 21A 5'-flanking DNA and includes 21A sequences, the designation of 21A as a "pseudogene" merits reconsideration.
Highlights
Human adrenal steroid 21-hydroxylase (P450c21) cihsromosome 6p21.1 and are duplicated in tandem with the encoded by the CYP2lAl (21B) gene located in the C4A and C4B genes, which encode the two forms of the fourth class I11 region of the HLA locus
We previously showed that two additional genes, XA and XB, lie on the opposite strand of DNA overlapping the 3‘-ends of the 21A and 21B genes
We have identified a third pair of duplicated overlappinggenes in thislocus, termed YA and YB, whose transcriptional orientation is the same as 21A and 21B and opposite to XA and XB
Summary
Temperature and twice for 15 min at 65"C. Positive plaques were Cloning of YA cDNAs-Northern blots of fetaladrenal picked and purified by two additional rounds of plating and probing. Similar transcripts are seen on long exposures of Northern blots of humanfetaladrenal RNA probed with 21B cDNA (Fig. 2, lune 2) (29). (Fig. 1, upper panel), to screen 350,000 clones of our unamplified cDNA library constructed from human fetal adrenal RNA. Clone YA-3 was 2.6 kb long and hada 5"sequence identical to thatof 21A, beginning at base -80 (numbered according to Ref. 6). This cDNA was Northern Blotting-Total RNA was prepared from human fetal identified as a 21A transcript because its first exon contained tissues quickly frozen in liquid Nz as described above. Parts of the six XB exons in this region (Fig. 1B)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
