TY - JOUR
T1 - Translational regulation is a control point in RUNX2/Cbfa1 gene expression
AU - Sudhakar, Sivasubramaniam
AU - Li, Ye
AU - Katz, Michael S.
AU - Elango, Narayanasamy
N1 - Funding Information:
We thank Dr. Yosiaki Ito (Kyoto University, Japan) for his gift of pKSαA1 DNA, Dr. G. D. Roodman (University of Pittsburgh Cancer Institute) for ST2 and MC3T3-E1 cell lines, and Dr. Gokul Das (University of Texas Health Science Center at San Antonio) for SaOS-2 and U2OS cell lines. This work was supported by grants from the American Federation for Aging Research and Veterans Integrated Service Network 17 (to N. Elango) and from the Department of Veterans Affairs (to M. S. Katz).
PY - 2001/11/30
Y1 - 2001/11/30
N2 - Runt-related transcription factor-2 (RUNX2)/core binding factor a1 (Cbfa1) is implicated in the regulation of osteoblast differentiation and osteoblast-specific gene expression. Mutations in RUNX2 cause the bone disease cleidocranial dysplasia, which is characterized by multiple skeletal defects. RUNX2 is expressed as two isoforms (type-I and type-II) encoded by two different mRNAs. We report here the detection of both mRNAs in osteoblastic cells and osteoblast precursors as well as nonosteoblastic cells. Surprisingly, however, osteoblast precursors and nonosteoblastic cells express no RUNX2 protein; mature osteoblasts express both isoforms, while less mature osteoblastic cells express only type-I protein. Northern blot analysis of RNA isolated from polysomes and ribonucleoprotein particles demonstrated that RUNX2 mRNA is polysome-associated in osteoblastic cells but polysome-free in osteoblast precursors. These results suggest that (a) RUNX2 mRNAs are expressed but dormant in osteoblast precursors and nonosteoblastic cells, (b) RUNX2 gene expression is controlled at the translational level, and (c) the expression of individual protein isoforms of RUNX2 is differentiation stage specific. Thus, differentiation of cells along the osteoblast lineage appears to be regulated at the level of RUNX2 mRNA translation.
AB - Runt-related transcription factor-2 (RUNX2)/core binding factor a1 (Cbfa1) is implicated in the regulation of osteoblast differentiation and osteoblast-specific gene expression. Mutations in RUNX2 cause the bone disease cleidocranial dysplasia, which is characterized by multiple skeletal defects. RUNX2 is expressed as two isoforms (type-I and type-II) encoded by two different mRNAs. We report here the detection of both mRNAs in osteoblastic cells and osteoblast precursors as well as nonosteoblastic cells. Surprisingly, however, osteoblast precursors and nonosteoblastic cells express no RUNX2 protein; mature osteoblasts express both isoforms, while less mature osteoblastic cells express only type-I protein. Northern blot analysis of RNA isolated from polysomes and ribonucleoprotein particles demonstrated that RUNX2 mRNA is polysome-associated in osteoblastic cells but polysome-free in osteoblast precursors. These results suggest that (a) RUNX2 mRNAs are expressed but dormant in osteoblast precursors and nonosteoblastic cells, (b) RUNX2 gene expression is controlled at the translational level, and (c) the expression of individual protein isoforms of RUNX2 is differentiation stage specific. Thus, differentiation of cells along the osteoblast lineage appears to be regulated at the level of RUNX2 mRNA translation.
KW - Isoforms
KW - Osteoblast differentiation
KW - RUNX2 transcription factor
KW - Translational regulation
KW - Type-specific antibodies
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U2 - 10.1006/bbrc.2001.6033
DO - 10.1006/bbrc.2001.6033
M3 - Article
C2 - 11716520
AN - SCOPUS:0035976775
VL - 289
SP - 616
EP - 622
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -