Characterization of the rat Star gene that encodes the predominant 3.5- kilobase pair mRNA

Noritaka Ariyoshi, Young Cheul Kim, Irina Artemenko, Kalyan K. Bhattacharyya, Colin R. Jefcoate

Research output: Contribution to journalArticle

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Abstract

The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat adrenal Star gene is transcribed as a 3.5- kilobase pair (kb) and 1.6-kb mRNA with the larger mRNA predominating (~85% of total) in vivo. Hypophysectomy (HPX) produced a 3-5-fold decrease in Star mRNA along with a loss of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold. Adrenocorticotropic hormone (ACTH) treatment of HPX rats maximally stimulated steroidogenesis rates within 5 min with over 10-fold elevation of steady state blood levels occurring within 10 min. For intact rats there was a 5 - 10-fold larger increase, paralleling previously observed elevations of cholesterol-cytochrome P450scc association and metabolism in subsequently isolated adrenal mitochondria. ACTH did not increase either total STAR protein or a group of modified forms until at least 30 min after completion of acute stimulation, indicating that elevated translation of STAR protein cannot alone mediate this acute stimulation. Parallel slow changes in STAR protein and corticosterone formation after ACTH treatment are consistent with participation of STAR forms as co-regulators of these hormonal responses. ACTH stimulation of HPX rats increased Star mRNA by 2.5-fold within 20 min and by 4.5-fold after 1 h, thus preceding the rise in the STAR protein. A 3.5-kb Star cDNA clone isolated from a rat adrenal cDNA library exhibited a 0.9-kb open reading frame and a 2.5-kb 3'-untranslated region (3'-UTR). The open reading frame sequence differed only 12 amino acids from that of the mouse Star. The rat Star gene seven exons with exon 7 encoding the entire 2.5 kb of 3'-UTR of the 3.5-kb mRNA. The 3'-UTR sequence suggests that 1.6- and 3.5-kb mRNA are formed by an alternative usage of different polyadenylation signals. Multiple UUAUUUA(U/A)(U/A) motifs also suggest additional regulation through this extended 3'-UTR. Although elevation of STAR protein by ACTH does not cause the acute increase in adrenal cholesterol metabolism, changes in the turnover or distribution of an active STAR subfraction cannot be excluded.

Original languageEnglish
Pages (from-to)7610-7619
Number of pages10
JournalJournal of Biological Chemistry
Volume273
Issue number13
DOIs
Publication statusPublished - Mar 27 1998
Externally publishedYes

Fingerprint

Stars
Rats
Genes
Messenger RNA
Adrenocorticotropic Hormone
3' Untranslated Regions
Cholesterol Side-Chain Cleavage Enzyme
Cholesterol
Proteins
Metabolism
Open Reading Frames
Exons
Hypophysectomy
Polyadenylation
Mitochondria
steroidogenic acute regulatory protein
Corticosterone
Gene Library
Blood
Complementary DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of the rat Star gene that encodes the predominant 3.5- kilobase pair mRNA. / Ariyoshi, Noritaka; Kim, Young Cheul; Artemenko, Irina; Bhattacharyya, Kalyan K.; Jefcoate, Colin R.

In: Journal of Biological Chemistry, Vol. 273, No. 13, 27.03.1998, p. 7610-7619.

Research output: Contribution to journalArticle

Ariyoshi, Noritaka ; Kim, Young Cheul ; Artemenko, Irina ; Bhattacharyya, Kalyan K. ; Jefcoate, Colin R. / Characterization of the rat Star gene that encodes the predominant 3.5- kilobase pair mRNA. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 13. pp. 7610-7619.
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abstract = "The steroidogenic acute regulatory protein (STAR) participates in steroidogenesis through the mitochondrial transfer of cholesterol to cytochrome P450scc. The rat adrenal Star gene is transcribed as a 3.5- kilobase pair (kb) and 1.6-kb mRNA with the larger mRNA predominating (~85{\%} of total) in vivo. Hypophysectomy (HPX) produced a 3-5-fold decrease in Star mRNA along with a loss of adrenal steroids, whereas P450scc mRNA decreased by less than 2-fold. Adrenocorticotropic hormone (ACTH) treatment of HPX rats maximally stimulated steroidogenesis rates within 5 min with over 10-fold elevation of steady state blood levels occurring within 10 min. For intact rats there was a 5 - 10-fold larger increase, paralleling previously observed elevations of cholesterol-cytochrome P450scc association and metabolism in subsequently isolated adrenal mitochondria. ACTH did not increase either total STAR protein or a group of modified forms until at least 30 min after completion of acute stimulation, indicating that elevated translation of STAR protein cannot alone mediate this acute stimulation. Parallel slow changes in STAR protein and corticosterone formation after ACTH treatment are consistent with participation of STAR forms as co-regulators of these hormonal responses. ACTH stimulation of HPX rats increased Star mRNA by 2.5-fold within 20 min and by 4.5-fold after 1 h, thus preceding the rise in the STAR protein. A 3.5-kb Star cDNA clone isolated from a rat adrenal cDNA library exhibited a 0.9-kb open reading frame and a 2.5-kb 3'-untranslated region (3'-UTR). The open reading frame sequence differed only 12 amino acids from that of the mouse Star. The rat Star gene seven exons with exon 7 encoding the entire 2.5 kb of 3'-UTR of the 3.5-kb mRNA. The 3'-UTR sequence suggests that 1.6- and 3.5-kb mRNA are formed by an alternative usage of different polyadenylation signals. Multiple UUAUUUA(U/A)(U/A) motifs also suggest additional regulation through this extended 3'-UTR. Although elevation of STAR protein by ACTH does not cause the acute increase in adrenal cholesterol metabolism, changes in the turnover or distribution of an active STAR subfraction cannot be excluded.",
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