18542101

pubmed:Citation

9

We have previously reported that the human ACAT1 gene produces a chimeric mRNA through the interchromosomal processing of two discontinuous RNAs transcribed from chromosomes 1 and 7. The chimeric mRNA uses AUG(1397-1399) and GGC(1274-1276) as translation initiation codons to produce normal 50-kDa ACAT1 and a novel enzymatically active 56-kDa isoform, respectively, with the latter being authentically present in human cells, including human monocyte-derived macrophages. In this work, we report that RNA secondary structures located in the vicinity of the GGC(1274-1276) codon are required for production of the 56-kDa isoform. The effects of the three predicted stem-loops (nt 1255-1268, 1286-1342 and 1355-1384) were tested individually by transfecting expression plasmids into cells that contained the wild-type, deleted or mutant stem-loop sequences linked to a partial ACAT1 AUG open reading frame (ORF) or to the ORFs of other genes. The expression patterns were monitored by western blot analyses. We found that the upstream stem-loop(1255-1268) from chromosome 7 and downstream stem-loop(1286-1342) from chromosome 1 were needed for production of the 56-kDa isoform, whereas the last stem-loop(1355-1384) from Chromosome 1 was dispensable. The results of experiments using both monocistronic and bicistronic vectors with a stable hairpin showed that translation initiation from the GGC(1274-1276) codon was mediated by an internal ribosome entry site (IRES). Further experiments revealed that translation initiation from the GGC(1274-1276) codon requires the upstream AU-constituted RNA secondary structure and the downstream GC-rich structure. This mechanistic work provides further support for the biological significance of the chimeric nature of the human ACAT1 transcript.

http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-10196189, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-10593897, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-10606268, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-10660678, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-11264983, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-11345437, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-11353332, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-11399774, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-12824337, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-15024068, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-15253151, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-15319423, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-15353128, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-15459663, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-15572659, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-16213112, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-16274362, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-16518538, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-16607284, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-16790843, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-17698501, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-2601712, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-3045756, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-3335499, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-7493995, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-7657611, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-8395052, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-8407899, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-8943341, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-8943342, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-9242919, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-9420332, http://linkedlifedata.com/resource/pubmed/commentcorrection/18542101-9774635

http://linkedlifedata.com/resource/pubmed/journal/9425763

http://linkedlifedata.com/resource/pubmed/chemical/ACAT1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Acetyl-CoA C-Acetyltransferase, http://linkedlifedata.com/resource/pubmed/chemical/Codon, http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms, http://linkedlifedata.com/resource/pubmed/chemical/RNA, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger

Sep

pubmed-author:ChangCatherine C YCC, pubmed-author:ChangTa-YuanTY, pubmed-author:ChenJiaJ, pubmed-author:ElfatihMM, pubmed-author:HuGuang-JingGJ, pubmed-author:LiBo-LiangBL, pubmed-author:SongBao-LiangBL, pubmed-author:XiongYingY, pubmed-author:YangLiL, pubmed-author:YangXin-YingXY, pubmed-author:ZhaoXiao-NanXN

18

Y

2011-7-28