Nagarajan L, Narayana L
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Biochem Biophys Res Commun. 1993 Jan 29;190(2):435-9. doi: 10.1006/bbrc.1993.1066.
Levels of the mRNA for PIM-1, a protooncogene encoding a cytoplasmic serine threonine kinase show a wide variation among tissues and cell lines, although this gene is transcribed from a GC- rich housekeeping promoter. Previous studies have failed to identify tissue specific elements in the PIM-1 promoter raising the possibility that these elements might reside within the gene. Transient transfections of Luciferase reporter gene constructs into the chronic myelogenous leukemia cell line K562 (which expresses high levels of PIM-1 mRNA) demonstrate that the 1.7kbp PIM-1 promoter sequences alone were three times more efficient than constructs driven by the promoter+PIM-1 genomic sequences. Nuclear run on assays of nascent RNA from K562 cells revealed premature transcriptional termination within the PIM-1 gene. Thus, PIM-1 gene may be constitutively transcribed in all tissues and transcriptional attenuation could be one of the mechanisms regulating the observed differences in steady state levels of mRNA.
原癌基因PIM-1编码一种细胞质丝氨酸苏氨酸激酶,其mRNA水平在不同组织和细胞系中存在很大差异,尽管该基因是从富含GC的管家启动子转录而来。先前的研究未能在PIM-1启动子中鉴定出组织特异性元件,这增加了这些元件可能存在于基因内部的可能性。将荧光素酶报告基因构建体瞬时转染到慢性粒细胞白血病细胞系K562(该细胞系表达高水平的PIM-1 mRNA)中,结果表明单独的1.7kbp PIM-1启动子序列的效率比由启动子+PIM-1基因组序列驱动的构建体高三倍。对来自K562细胞的新生RNA进行的核转录分析揭示了PIM-1基因内的过早转录终止。因此,PIM-1基因可能在所有组织中组成性转录,转录衰减可能是调节观察到的mRNA稳态水平差异的机制之一。