ACAT1 mRNA explained

ACAT1 mRNA
Symbol:ACAT1
Rfam:RF01495
Go:0006446
So:0005836

Human acetyl-coA cholesterol acyltransferase (ACAT1) gene produces a chimeric mRNA through the interchromosomal processing of two discontinuous RNAs transcribed from chromosomes 1 and 7.[1] This chimeric mRNA uses AUG as a translation initiation codon to produce the normal 50-kDa ACAT1 protein but used an alternative translation initiation codon, GGC, to produce the novel enzymatically active 56-kDa isoform.

Mutagenesis and mass spectrometry identified the alternative initiation codon as the start codon for the novel 56-kDa protein and its location was mapped to a region located upstream of the AUG initiation codon. Three stem loop structures have been predicted to surround the GCC initiation codon and are known as SL1 to SL3. Mutations that disrupted these stem-loop structures showed that SL1 and SL2 as required for translation initiation from the GGC codon but SL3 has no effect on translation efficiency. Translation initiation from the GGC codon was shown to be is mediated by an internal ribosome entry site (IRES) which requires SL1 located upstream of the IRES and SL2 located downstream.[2] This study also showed that SL3 influences the choice of downstream AUG translation initiation codons that will produce the normal 50-KDa human ACAT1 protein.[3]

Notes and References

  1. Yang L, Lee O, Chen J, Chen J, Chang CC, Zhou P, Wang ZZ, Ma HH, Sha HF, Feng JX, Wang Y, Yang XY, Wang L, Dong R, Ornvold K, Li BL, Chang TY . Human acyl-coenzyme A:cholesterol acyltransferase 1 (acat1) sequences located in two different chromosomes (7 and 1) are required to produce a novel ACAT1 isoenzyme with additional sequence at the N terminus . The Journal of Biological Chemistry . 279 . 44 . 46253–62 . October 2004 . 15319423 . 10.1074/jbc.M408155200 . Free full text . free .
  2. Chen J, Zhao XN, Yang L, Hu GJ, Lu M, Xiong Y, Yang XY, Chang CC, Song BL, Chang TY, Li BL . RNA secondary structures located in the interchromosomal region of human ACAT1 chimeric mRNA are required to produce the 56-kDa isoform . Cell Research . 18 . 9 . 921–36 . September 2008 . 18542101 . 3086790 . 10.1038/cr.2008.66 .
  3. Yang L, Chen J, Chang CC, Yang XY, Wang ZZ, Chang TY, Li BL . A stable upstream stem-loop structure enhances selection of the first 5'-ORF-AUG as a main start codon for translation initiation of human ACAT1 mRNA . Acta Biochimica et Biophysica Sinica . 36 . 4 . 259–68 . April 2004 . 15253151 . 10.1093/abbs/36.4.259 . Free full text . https://web.archive.org/web/20160303175633/http://www.abbs.info/fulltxt/36-4/36040259.htm . dead . 2016-03-03 .