Hormone-dependent expression of a steroidogenic acute regulatory protein natural antisense transcript in MA-10 mouse tumor Leydig cells

Authors
Castillo, Ana Fernanda; Fan, Jinjiang; Papadopoulos, Vassilios; Podesta, Ernesto Jorge
Publication Year
2011
Language
English
Format
article
Status
Published version
Description
Cholesterol transport is essential for many physiological processes, including steroidogenesis. In steroidogenic cells hormone-induced cholesterol transport is controlled by a protein complex that includes steroidogenic acute regulatory protein (StAR). Star is expressed as 3.5-, 2.8-, and 1.6-kb transcripts that differ only in their 3′-untranslated regions. Because these transcripts share the same promoter, mRNA stability may be involved in their differential regulation and expression. Recently, the identification of natural antisense transcripts (NATs) has added another level of regulation to eukaryotic gene expression. Here we identified a new NAT that is complementary to the spliced Star mRNA sequence. Using 5′ and 3′ RACE, strand-specific RT-PCR, and ribonuclease protection assays, we demonstrated that Star NAT is expressed in MA-10 Leydig cells and steroidogenic murine tissues. Furthermore, we established that human chorionic gonadotropin stimulates Star NAT expression via cAMP. Our results show that sense-antisense Star RNAs may be coordinately regulated since they are co-expressed in MA-10 cells. Overexpression of Star NAT had a differential effect on the expression of the different Star sense transcripts following cAMP stimulation. Meanwhile, the levels of StAR protein and progesterone production were downregulated in the presence of Star NAT. Our data identify antisense transcription as an additional mechanism involved in the regulation of steroid biosynthesis.
Fil: Castillo, Ana Fernanda. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquimica Humana. Catedra de Quimica Biologica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Fan, Jinjiang. Mc Gill University; Canadá
Fil: Papadopoulos, Vassilios. Mc Gill University; Canadá
Fil: Podesta, Ernesto Jorge. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Bioquímica Humana; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Subject
Steroidogenic acute regulatory protein
StAR
Natural antisense transcript
NAT
Steroid synthesis
Gene expression
Hormonal regulation
Bioquímica y Biología Molecular
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/15191