Coordinate Developmental Regulation of High and Low Molecular Weight mRNAs for Rat Insulin-Like Growth Factor II

Insulin-like growth factor II (IGF-II) is a mitogenic polypeptide that is thought to play a role in fetal growth and development. To study the hormonal and developmental regulation of IGF-II gene expression, we have isolated a cDNA clone for rat IGF-II (rIGF-II) from a 12S [1.2-kilobase-pair (kbp)]...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 12; pp. 4519 - 4523
Main Authors:	Graham, Dale E., Rechler, Matthew M., Brown, Alexandra L., Frunzio, Rodolfo, Romanus, Joyce A., Bruni, C. Bruno, Whitfield, Harvey J., Nissley, S. Peter, Seelig, Steven, Berry, Susan
Format:	Journal Article
Language:	English
Published:	Washington, DC National Academy of Sciences of the United States of America 01-06-1986 National Acad Sciences
Subjects:	Animals Biological and medical sciences Cell Compartmentation Cell Line Cell-Free System Cloning, Molecular Complementary DNA DNA - genetics Fundamental and applied biological sciences. Psychology Gels Gene expression Gene Expression Regulation Genetic hybridization Insulin-Like Growth Factor II - genetics Introns Liver Liver - embryology Liver - physiology Messenger RNA Molecular and cellular biology Molecular genetics Molecular Weight Nucleic Acid Hybridization Protein Biosynthesis Rats RNA RNA probes RNA, Messenger - genetics Somatomedins - genetics Transcription, Genetic Vertebrata Regulation(control) Mammalia Messenger RNA Splicing Rat Animal Rodentia Development Somatomedin Gene expression
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Summary:	Insulin-like growth factor II (IGF-II) is a mitogenic polypeptide that is thought to play a role in fetal growth and development. To study the hormonal and developmental regulation of IGF-II gene expression, we have isolated a cDNA clone for rat IGF-II (rIGF-II) from a 12S [1.2-kilobase-pair (kbp)] fraction of mRNA from a rat liver cell line (BRL-3A) that directs the cell-free synthesis of pre-pro-rIGF-II. In the present study, the rIGF-II probe was used to determine the size of IGF-II RNA. Surprisingly, in BRL-3A cells and in neonatal liver, the probe hybridized under stringent conditions 10-20 times more strongly to a larger (4 kbp) RNA than to 1.2-kbp RNA. The 4-kbp RNA is almost exclusively cytoplasmic and is colinear with a 551-base fragment of the rIGF-II cDNA insert containing coding and 3′ noncoding regions. The 4-kbp and 1.2-kbp RNA species are regulated coordinately with developmental age, being high in liver from neonatal rats but not detectable in liver from older animals, suggesting that both IGF-II mRNA species arise from a single primary transcript by alternative RNA processing. Although oligodeoxynucleotide hybridization and S1 nuclease protection experiments suggest that the 4-kbp RNA contains an intact protein-coding region, fractions enriched in 4-kbp RNA do not direct the translation of pre-pro-rIGF-II in vitro. This may indicate that the 4-kbp RNA specifies an altered protein product that has not yet been recognized, or alternatively that it contains a normal protein-coding region but requires further RNA processing to be activated for translation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.83.12.4519