The novel OCT4 spliced variant OCT4B1 can generate three protein isoforms by alternative splicing into OCT4B

Yuan Gao; Xia Wang; Jin Han; Zhifeng Xiao; Bing Chen; Guannan Su; Jianwu Dai

doi:10.1016/S1673-8527(09)60065-5

Volume 37 Issue 7

Jul. 2010

Turn off MathJax

Article Contents

Article Navigation > Journal of Genetics and Genomics > 2010 > 37(7): 461-465

PDF( 246 KB)

The novel OCT4 spliced variant OCT4B1 can generate three protein isoforms by alternative splicing into OCT4B

doi: 10.1016/S1673-8527(09)60065-5

Yuan Gao^{a, b, #},
Xia Wang^{a, #},
Jin Han^a,
Zhifeng Xiao^a,
Bing Chen^a,
Guannan Su^a,
Jianwu Dai^a

a
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China
b
The Graduate School, Chinese Academy of Sciences, Beijing 100190, China

More Information

Corresponding author: E-mail address: jwdai@genetics.ac.cn (Jianwu Dai)
Received Date: 2010-03-17
Accepted Date: 2010-05-12
Rev Recd Date: 2010-05-06

Available Online: 2010-07-24

Publish Date: 2010-07-20

Abstract

Abstract

OCT4 is one of the key transcription factors in maintaining the pluripotency and self-renewal of embryonic stem (ES) cells. HumanOCT4 can generate two isoforms OCT4A and OCT4B by alternative splicing. OCT4B1 is a recently discovered novel OCT4 spliced variant, which has been considered as a putative marker of stemness. Compared with the OCT4B mRNA, OCT4B1 mRNA is generated by retaining intron 2 as a cryptic exon which contains a TGA stop codon in it. As a result, the protein product of OCT4B1 mRNA could be truncated. Interestingly, we present here that OCT4B1 can indirectly produce the same protein products as OCT4B. We have demonstrated that OCT4B1 mRNA can be spliced into OCT4B mRNA, and encode three protein isoforms. The splicing of OCT4B1 mRNA into OCT4B mRNA can be remarkably inhibited by the mutation of the classical splicing site. Our result suggests that OCT4B mRNA may originate from OCT4B1 mRNA by alternative splicing.
- OCT4,
- alternative splicing,
- alternative translation initiation,
- stress

These authors contributed equally to this work.

FullText(HTML)

References(13)

References

[1]	Atlasi, Y., Mowla, S.J., Ziaee, S.A. et al. Stem Cells, 26 (2008),pp. 3068-3074
[2]	Cauffman, G., Van de Velde, H., Liebaers, I. et al. Mol. Hum. Reprod., 11 (2005),pp. 173-181
[3]	Cauffman, G., Liebaers, I., Van Steirteghem, A. et al. POU5F1 isoforms show different expression patterns in human embryonic stem cells and preimplantation embryos Stem Cells, 24 (2006),pp. 2685-2691
[4]	Ho, S.N., Hunt, H.D., Horton, R.M. et al. Site-directed mutagenesis by overlap extension using the polymerase chain reaction Gene, 77 (1989),pp. 51-59
[5]	Irimia, M., Penny, D., Roy, S.W. Coevolution of genomic intron number and splice sites Trends Genet., 23 (2007),pp. 321-325
[6]	Keller, E.B., Noon, W.A. Intron splicing: a conserved internal signal in introns of animal pre-mRNAs. Proc. Natl. Acad. Sci USA, 81 (1984),pp. 7417-7420
[7]	Keller, E.B., Noon, W.A. Nucleic Acids Res., 13 (1985),pp. 4971-4981
[8]	Kotoula, V., Papamichos, S.I., Lambropoulos, A.F. Revisiting OCT4 expression in peripheral blood mononuclear cells Stem Cells, 26 (2008),pp. 290-291
[9]	Papamichos, S.I., Kotoula, V., Tarlatzis, B.C. et al. Mol. Hum. Reprod., 15 (2009),pp. 269-270
[10]	Scholer, H.R., Ruppert, S., Suzuki, N. et al. New type of POU domain in germ line-specific protein Oct-4 Nature, 344 (1990),pp. 435-439
[11]	Takeda, J., Seino, S., Bell, G.I. Human Oct3 gene family: cDNA sequences, alternative splicing, gene organization, chromosomal location, and expression at low levels in adult tissues Nucleic Acids Res., 20 (1992),pp. 4613-4620
[12]	Wang, X., Dai, J. Isoforms of OCT4 contribute to the confusing diversity in stem cell biology Stem Cells, 28 (2010),pp. 885-893
[13]	Wang, X., Zhao, Y., Xiao, Z. et al. Alternative translation of OCT4 by an internal ribosome entry site and its novel function in stress response Stem Cells, 27 (2009),pp. 1265-1275