An effect of androgens on the length of the poly(A)-tail and alternative splicing cause size heterogeneity of the messenger ribonucleic acids encoding cystatin-related protein.
The 22-kilodalton glycoprotein, expressed in the rat ventral prostate under the influence of androgens, is structurally a cystatin-related protein (CRP), as has been shown by copy DNA sequencing. In fact, two slightly different forms (CRP-1 and CRP-2) are expressed in the prostate; one of them (CRP-1) is also expressed in the exorbital lacrymal gland. In both glands, the CRP-1 messenger RNA (mRNA)s are androgen regulated. Moreover, androgens also influence the size of these mRNAs, which show marked heterogeneity (from 760-950 nucleotides). Indeed, the smaller forms are predominant in castrated animals, whereas the large forms are observed immediately after androgen induction. Hybridization with oligo(dT) followed by ribonuclease H treatment revealed that differences in length of the poly(A)-tail are responsible for this effect of androgens. Indeed, two well defined forms of CRP mRNA subsisted after removal of the poly(A)-tail by this treatment. In the less abundant shorter form (CRP-1 delta), 123 nucleotides are deleted by alternative splicing at the junction between the third and the fourth exon. The variant mRNA encodes a truncated protein, wherein the last 27 amino acids are replaced by a hydrophobic stretch of 8 amino acids. No alternative splicing was observed for the CRP-2 mRNA.
Vercaeren
I
I
Laboratorium voor Experimentele Geneeskunde en Endocrinologie, Faculteit Geneeskunde, Catholic University of Leuven, Belgium.
Winderickx
J
J
Devos
A
A
Peeters
B
B
Heyns
W
W
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D016375:Antisense Elements (Genetics); D001483:Base Sequence; D003001:Cloning, Molecular; D015891:Cystatins; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D009919:Orchiectomy; D011061:Poly A / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011467:Prostate / Q000187:drug effects / Q000502:physiology*; D011506:Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013739:Testosterone / Q000494:pharmacology*
C079958:Andpro protein, rat; D016375:Antisense Elements (Genetics); D015891:Cystatins; D009838:Oligodeoxyribonucleotides; C484121:P22k15 protein, rat; D011506:Proteins; D012333:RNA, Messenger; D011061:Poly A; D013739:Testosterone; D012313:RNA