HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bab, I. Articles by Frenkel, B. Search for Related Content PubMed PubMed Citation Articles by Bab, I. Articles by Frenkel, B. Social Bookmarking                      What's this?

J Biol Chem, Vol. 274, Issue 20, 14474-14481, May 14, 1999

Biosynthesis of Osteogenic Growth Peptide via Alternative Translational Initiation at AUG₈₅ of Histone H4 mRNA

Itai Bab, Elisheva Smith^§, Hanna Gavish, Malka Attar-Namdar, Michael Chorev^¶, Yu-Chen Chen, Andrash Muhlrad, Mark J. Birnbaum, Gary Stein^**, and Baruch Frenkel^§

From the  Bone Laboratory, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel, the ^§ Departments of Orthopaedic Surgery and Biochemistry and Molecular Biology and the Institute for Genetic Medicine, University of Southern California School of Medicine, Los Angeles, California 90033, the ^¶ Division of Bone and Mineral Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, the  Department of Biology, Merrimack College, North Andover, Massachusetts 01845, and the ^** Department of Cell Biology, University of Massachusetts Medical Center, Worcester, Massachusetts 01655

The osteogenic growth peptide (OGP) is an extracellular mitogen identical to the histone H4 (H4) COOH-terminal residues 90-103, which regulates osteogenesis and hematopoiesis. By Northern analysis, OGP mRNA is indistinguishable from H4 mRNA. Indeed, cells transfected with a construct encoding [His¹⁰²]H4 secreted the corresponding [His¹³]OGP. These results suggest production of OGP from H4 genes. Cells transfected with H4-chloramphenicol acetyltransferase (CAT) fusion genes expressed both "long" and "short" CAT proteins. The short CAT was retained following an ATG  TTG mutation of the H4 ATG initiation codon, but not following mutation of the in-frame internal ATG₈₅ codon, which, unlike ATG₁, resides within a perfect context for translational initiation. These results suggest that a PreOGP is translated starting at AUG₈₅. The translational initiation at AUG₈₅ could be inhibited by optimizing the nucleotide sequence surrounding ATG₁ to maximally support upstream translational initiation, thus implicating leaky ribosomal scanning in usage of the internal AUG. Conversion of the predicted PreOGP to OGP was shown in a cell lysate system using synthetic [His¹⁰²]H4-(85-103) as substrate. Together, our results demonstrate that H4 gene expression diverges at the translational level into the simultaneous parallel production of both H4, a nuclear structural protein, and OGP, an extracellular regulatory peptide.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				D. Matsuda and T. W. Dreher Close spacing of AUG initiation codons confers dicistronic character on a eukaryotic mRNA RNA, July 1, 2006; 12(7): 1338 - 1349. [Abstract] [Full Text] [PDF]

				E. Smith, T. E. Meyerrose, T. Kohler, M. Namdar-Attar, N. Bab, O. Lahat, T. Noh, J. Li, M. W. Karaman, J. G. Hacia, et al. Leaky ribosomal scanning in mammalian genomes: significance of histone H4 alternative translation in vivo Nucleic Acids Res., March 1, 2005; 33(4): 1298 - 1308. [Abstract] [Full Text] [PDF]

				M. M. Martin, B. M. Willardson, G. F. Burton, C. R. White, J. N. McLaughlin, S. M. Bray, J. W. Ogilvie Jr., and T. S. Elton Human Angiotensin II Type 1 Receptor Isoforms Encoded by Messenger RNA Splice Variants Are Functionally Distinct Mol. Endocrinol., February 1, 2001; 15(2): 281 - 293. [Abstract] [Full Text]