Isoform/variant mRNAs for sex steroid hormone receptors in humans

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Abstract

The open reading frames of human sex steroid hormone receptors (hSSHRs) are composed of eight exons. In addition, the presence of various exons – including 5′-untranslated exons, alternative coding exons and novel ‘intronic’ exons – has been demonstrated in the genes encoding hSSHRs. The isoform/variant hSSHR mRNAs generated from thes e exons can be tentatively classified into seven types. In type 1, different mRNAs are generated with the use of alternative transcription start sites. In type 2, one or more exons are skipped. In type 3, one or more exons are duplicated. In type 4, distinct mRNAs containing different 5′-untranslated exon(s) are synthesized. In type 5, distinct mRNAs possessing different coding exon(s) are generated. In type 6, mRNA is synthesized by intronic exons and coding exons 4/5–8. In type 7, mRNA with insertion of intronic exon(s) is generated. Here, we review the isoform/variant hSSHR mRNAs and the structure of the genes encoding them.

Section snippets

Structure of the gene encoding ERα

In addition to coding exons 1–8 4, 5, eight untranslated 5′-exons in the upstream region of exon 1 6, 7, 8, 9, 10, 11, 12, and an ‘intronic’ exon S located between exons 3 and 4 [13] are identified in the gene encoding human ERα (Fig. 1).

Isoform/variant mRNAs encoding ERα

In mRNA encoding human ERα, type 2, 3, 4 and 6 isoform/variant transcripts have been reported. In addition, the ‘type 7-like’ mRNA variant of ERα that is generated by a point mutation in the intron located between exons 5 and 6 is also discussed.

Type 2: Since

Structure of the gene encoding ERβ

The coding region of the gene encoding human ERβ comprises exons 1–7 28, 29 and five alternative exon 8s 30, 31, 32. In addition, seven untranslated 5′-exons in the upstream region of exon 1 32, 33, and an ‘intronic’ exon M between exons 4 and 5 [34] have been identified (Fig. 2).

Isoform/variant mRNAs encoding ERβ

In mRNA encoding human ERβ, types 2, 4, 5 and 6 isoform/variant transcripts have been reported. The type 7 isoform mRNA reported in mRNA encoding rodent ERβ is also discussed here 35, 36, 37. It has been reported that

Structure of the gene encoding PR

The coding region of the gene encoding human PR comprises exons 1–8 45, 46, 47. In addition, ‘intronic’ exons have also been identified: exons T [48] and S [49] between exons 3 and 4; and exons i45a [50] and i45b [50] between exons 4 and 5 (Fig. 3).

Isoform/variant mRNAs encoding PR

In mRNA encoding the human PR, isoform/variant transcript types 1, 2, 6 and 7 have been identified.

Type 1: By using upstream transcription start sites and downstream ones, PR isoform B and A mRNAs are generated. The longer PR isoform B mRNA and the

Structure of the gene encoding AR

The open reading frame of the gene encoding human AR comprises exons 1–8 59, 60, 61 (Fig. 4). Unlike the other genes encoding human SSHRs, no reports on 5′-untranslated exons, ‘intronic’ exons or alternative coding exons of the gene encoding human AR are currently available.

Isoform/variant mRNAs encoding AR

In mRNA encoding the human AR, only type 1 and type 2 isoform/variant transcripts have been identified. Many variant mRNAs are generated in humans, especially in cases of androgen insensitivity syndrome 62, 63; however, most

Conclusions

Human cDNAs encoding SSHRs, ERα [4], PR [45] and AR 59, 60 were cloned in the mid-1980s, and the genomic organization of the coding regions of these genes was clarified by the late 1980s 5, 47, 61. There have since been several landmark studies of isoform/variant mRNAs encoding SSHRs. First, an untranslated exon was identified in the gene encoding human ERα 6, 7, 8, 9, 10, 11, 12, and thereafter, various untranslated 5′-exons were recognized in the genes encoding ERα and ERβ. Second,

Acknowledgements

The authors thank Dr Selma M Soyal for providing the information on the genomic location of the PR exons T and S. This work was supported by grant No. 08671879, and No. 11671605 to SH from the Japanese Ministry of Education.

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