Osteocalcin is incompletely spliced in non-osseous tissues

Chaeyong Jung, Yen Chuan Ou, Fan Yeung, Henry F. Frierson, Chinghai Kao

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Osteocalcin (OC) is known to be a bone tissue-specific protein, expression of which is believed to be controlled by the OC promoter. In this communication, we provided evidence to demonstrate that tissue-specific expression of OC was also regulated at the RNA splicing level. We identified incompletely spliced variants of human OC mRNA, which retain one or more introns during RNA spicing, existing dominantly in non-osseous organs. Northern blot analysis identified two OC RNA transcripts expressed in normal human tissues, but the expression level of the transcripts varied between the tissues. Most non-osseous tissues expressed transcripts with higher molecular weight, prominent in ovary, kidney, pancreas, spleen, thymus, prostate, and testis, than the expected size of OC mRNA as seen in bone marrow. RT-PCR analysis identified up to six OC transcripts in most tissues tested except bone marrow. Sequence analysis showed that four of five RNA variants contained intron 1 in common and the dominant one contained all three introns. MG63, an osteoblastic osteosarcoma cell, expressed only the completely-spliced form of OC, whereas incompletely spliced RNA was dominant in most prostate tumor cells. Combined study of in situ hybridization and immunohistochemistry revealed that OC RNA was highly expressed in prostate tumor epithelial cells while only very low levels of protein were detected, which confirms that there are OC RNA variants in non-osseous tissues. In conclusion, we demonstrated that OC mRNA is also expressed in several non-osseous tissues. However, only bone preferentially underwent the complete splicing event of all three introns. The function of other splicing variants of OC mRNA needs to be further investigated.

Original languageEnglish
Pages (from-to)143-150
Number of pages8
JournalGene
Volume271
Issue number2
DOIs
StatePublished - Jun 27 2001

Fingerprint

Osteocalcin
RNA
Introns
Prostate
Messenger RNA
Bone Marrow
RNA Splicing
Bone and Bones
Osteosarcoma
Northern Blotting
Thymus Gland
In Situ Hybridization
Sequence Analysis
Testis
Pancreas
Ovary
Neoplasms
Proteins
Spleen
Molecular Weight

Keywords

  • Bone
  • Intron retention
  • RNA transcript
  • Splicing

ASJC Scopus subject areas

  • Genetics

Cite this

Osteocalcin is incompletely spliced in non-osseous tissues. / Jung, Chaeyong; Ou, Yen Chuan; Yeung, Fan; Frierson, Henry F.; Kao, Chinghai.

In: Gene, Vol. 271, No. 2, 27.06.2001, p. 143-150.

Research output: Contribution to journalArticle

Jung, C, Ou, YC, Yeung, F, Frierson, HF & Kao, C 2001, 'Osteocalcin is incompletely spliced in non-osseous tissues', Gene, vol. 271, no. 2, pp. 143-150. https://doi.org/10.1016/S0378-1119(01)00513-3
Jung, Chaeyong ; Ou, Yen Chuan ; Yeung, Fan ; Frierson, Henry F. ; Kao, Chinghai. / Osteocalcin is incompletely spliced in non-osseous tissues. In: Gene. 2001 ; Vol. 271, No. 2. pp. 143-150.
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AB - Osteocalcin (OC) is known to be a bone tissue-specific protein, expression of which is believed to be controlled by the OC promoter. In this communication, we provided evidence to demonstrate that tissue-specific expression of OC was also regulated at the RNA splicing level. We identified incompletely spliced variants of human OC mRNA, which retain one or more introns during RNA spicing, existing dominantly in non-osseous organs. Northern blot analysis identified two OC RNA transcripts expressed in normal human tissues, but the expression level of the transcripts varied between the tissues. Most non-osseous tissues expressed transcripts with higher molecular weight, prominent in ovary, kidney, pancreas, spleen, thymus, prostate, and testis, than the expected size of OC mRNA as seen in bone marrow. RT-PCR analysis identified up to six OC transcripts in most tissues tested except bone marrow. Sequence analysis showed that four of five RNA variants contained intron 1 in common and the dominant one contained all three introns. MG63, an osteoblastic osteosarcoma cell, expressed only the completely-spliced form of OC, whereas incompletely spliced RNA was dominant in most prostate tumor cells. Combined study of in situ hybridization and immunohistochemistry revealed that OC RNA was highly expressed in prostate tumor epithelial cells while only very low levels of protein were detected, which confirms that there are OC RNA variants in non-osseous tissues. In conclusion, we demonstrated that OC mRNA is also expressed in several non-osseous tissues. However, only bone preferentially underwent the complete splicing event of all three introns. The function of other splicing variants of OC mRNA needs to be further investigated.

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