ACAT1 mRNA

Last updated
ACAT1 mRNA
ACAT SS.png
Conserved secondary structure of ACAT1 mRNA
Identifiers
SymbolACAT1
Rfam RF01495
Other data
GO 0006446
SO 0005836
PDB structures PDBe

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.

ACAT1 protein-coding gene in the species Homo sapiens

Acetyl-CoA acetyltransferase, mitochondrial, also known as acetoacetyl-CoA thiolase, is an enzyme that in humans is encoded by the ACAT1 gene.

RNA family of large biological molecules

Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and DNA are nucleic acids, and, along with lipids, proteins and carbohydrates, constitute the four major macromolecules essential for all known forms of life. Like DNA, RNA is assembled as a chain of nucleotides, but unlike DNA it is more often found in nature as a single-strand folded onto itself, rather than a paired double-strand. Cellular organisms use messenger RNA (mRNA) to convey genetic information that directs synthesis of specific proteins. Many viruses encode their genetic information using an RNA genome.

Fusion protein Protein created by joining other proteins into a single polypeptide (usually by protein engineering)

Fusion proteins or chimeric (\kī-ˈmir-ik) proteins are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this fusion gene results in a single or multiple polypeptides with functional properties derived from each of the original proteins. Recombinant fusion proteins are created artificially by recombinant DNA technology for use in biological research or therapeutics. Chimeric or chimera usually designate hybrid proteins made of polypeptides having different functions or physico-chemical patterns. Chimeric mutant proteins occur naturally when a complex mutation, such as a chromosomal translocation, tandem duplication, or retrotransposition creates a novel coding sequence containing parts of the coding sequences from two different genes. Naturally occurring fusion proteins are commonly found in cancer cells, where they may function as oncoproteins. The bcr-abl fusion protein is a well-known example of an oncogenic fusion protein, and is considered to be the primary oncogenic driver of chronic myelogenous leukemia.

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]

Mutagenesis is a process by which the genetic information of an organism is changed, resulting in a mutation. It may occur spontaneously in nature, or as a result of exposure to mutagens. It can also be achieved experimentally using laboratory procedures. In nature mutagenesis can lead to cancer and various heritable diseases, but it is also a driving force of evolution. Mutagenesis as a science was developed based on work done by Hermann Muller, Charlotte Auerbach and J. M. Robson in the first half of the 20th century.

Mass spectrometry analytical technique based on determining mass to charge ratio of ions

Mass spectrometry (MS) is an analytical technique that ionizes chemical species and sorts the ions into a spectrum based on their mass-to-charge ratio. In simpler terms, a mass spectrum measures the masses within a sample. Mass spectrometry is used in many different fields and is applied to pure samples as well as complex mixtures.

The start codon is the first codon of a messenger RNA (mRNA) transcript translated by a ribosome. The start codon always codes for methionine in eukaryotes and a modified Met (fMet) in prokaryotes. The most common start codon is AUG.

Related Research Articles

Translation (biology) in biology, the process in which cellular ribosomes create proteins

In molecular biology and genetics, translation is the process in which ribosomes in the cytoplasm or ER synthesize proteins after the process of transcription of DNA to RNA in the cell's nucleus. The entire process is called gene expression.

The 5′ untranslated region is the region of an mRNA that is directly upstream from the initiation codon. This region is important for the regulation of translation of a transcript by differing mechanisms in viruses, prokaryotes and eukaryotes. While called untranslated, the 5′ UTR or a portion of it is sometimes translated into a protein product. This product can then regulate the translation of the main coding sequence of the mRNA. In many organisms, however, the 5′ UTR is completely untranslated, instead forming complex secondary structure to regulate translation. The 5′ UTR has been found to interact with proteins relating to metabolism; and proteins translate sequences within the 5′ UTR. In addition, this region has been involved in transcription regulation, such as the sex-lethal gene in Drosophila. Regulatory elements within 5′ UTRs have also been linked to mRNA export.

The Shine-Dalgarno (SD) Sequence is a ribosomal binding site in bacterial and archaeal messenger RNA, generally located around 8 bases upstream of the start codon AUG. The RNA sequence helps recruit the ribosome to the messenger RNA (mRNA) to initiate protein synthesis by aligning the ribosome with the start codon. Once recruited, tRNA may add amino acids in sequence as dictated by the codons, moving downstream from the translational start site.

Prokaryotic translation is the process by which messenger RNA is translated into proteins in prokaryotes.

Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recycling.

<i>N</i>-Formylmethionine chemical compound

N-Formylmethionine (fMet) is a derivative of the amino acid methionine in which a formyl group has been added to the amino group. It is specifically used for initiation of protein synthesis from bacterial and organellar genes, and may be removed post-translationally.

The Kozak consensus sequence, Kozak consensus or Kozak sequence is a sequence which occurs on eukaryotic mRNA and has the consensus (gcc)gccRccAUGG. The Kozak consensus sequence plays a major role in the initiation of the translation process. The sequence was named after the scientist who discovered it, Marilyn Kozak.

Eukaryotic initiation factors (eIFs) are proteins or protein complexes involved in the initiation phase of eukaryotic translation. These proteins help stabilize the formation of ribosomal preinitiation complexes around the start codon and are an important input for post-transcription gene regulation. Several initiation factors form a complex with the small 40S ribosomal subunit and Met-tRNAiMet called the 43S preinitiation complex. Additional factors of the eIF4F complex recruit the 43S PIC to the five-prime cap structure of the mRNA, from which the 43S particle scans 5'-->3' along the mRNA to reach an AUG start codon. Recognition of the start codon by the Met-tRNAiMet promotes gated phosphate and eIF1 release to form the 48S preinitiation complex, followed by large 60S ribosomal subunit recruitment to form the 80S ribosome. There exist many more eukaryotic initiation factors than prokaryotic initiation factors, reflecting the greater biological complexity of eukaryotic translation. There are at least twelve eukaryotic initiation factors, composed of many more polypeptides, and these are described below.

A ribosome binding site, or ribosomal binding site (RBS), is a sequence of nucleotides upstream of the start codon of an mRNA transcript that is responsible for the recruitment of a ribosome during the initiation of protein translation. Mostly, RBS refers to bacterial sequences, although internal ribosome entry sites (IRES) have been described in mRNAs of eukaryotic cells or viruses that infect eukaryotes. Ribosome recruitment in eukaryotes is generally mediated by the 5' cap present on eukaryotic mRNAs.

Untranslated region

In molecular genetics, an untranslated region refers to either of two sections, one on each side of a coding sequence on a strand of mRNA. If it is found on the 5' side, it is called the 5' UTR, or if it is found on the 3' side, it is called the 3' UTR. mRNA is RNA that carries information from DNA to the ribosome, the site of protein synthesis (translation) within a cell. The mRNA is initially transcribed from the corresponding DNA sequence and then translated into protein. However, several regions of the mRNA are usually not translated into protein, including the 5' and 3' UTRs.

SOAT1 protein-coding gene in the species Homo sapiens

Sterol O-acyltransferase 1, also known as SOAT1, is an enzyme that in humans is encoded by the SOAT1 gene.

SOAT2 protein-coding gene in the species Homo sapiens

Sterol O-acyltransferase 2, also known as SOAT2, is an enzyme that in humans is encoded by the SOAT2 gene.

Leaky scanning is a mechanism used during the initiation phase of Eukaryotic translation that enables regulation of gene expression. During initiation, the small 40S ribosomal subunit "scans" or moves in a 5' --> 3' direction along the 5'UTR to locate a start codon to commence elongation. Sometimes, the scanning ribosome bypasses the initial AUG start codon and begins translation at further downstream AUG start codons. Translation in eukaryotic cells according to most scanning mechanisms occurs at the AUG start codon proximal to the 5' end of mRNA; however, the scanning ribosome may encounter an “unfavorable nucleotide context” around the start codon and continue scanning.

ACAT2 protein-coding gene in the species Homo sapiens

Acetyl-CoA acetyltransferase, cytosolic, also known as cytosolic acetoacetyl-CoA thiolase, is an enzyme that in humans is encoded by the ACAT2 gene

The Consensus Coding Sequence (CCDS) Project is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies. The CCDS project tracks identical protein annotations on the reference mouse and human genomes with a stable identifier, and ensures that they are consistently represented by the National Center for Biotechnology Information (NCBI), Ensembl, and UCSC Genome Browser. The integrity of the CCDS dataset is maintained through stringent quality assurance testing and on-going manual curation.

SUI1

In molecular biology, the single-domain protein SUI1 is a translation initiation factor often found in the fungus, Saccharomyces cerevisiae but it is also found in other eukaryotes and prokaryotes as well as archaea. It is otherwise known as Eukaryotic translation initiation factor 1 in eukaryotes or prokaryotic initiation factor-3 or YciH in bacteria.

Lily virus X (LVX) is a pathogenic ssRNA(+) plant virus of the family Alphaflexiviridae and the order Tymovirales. It is the type species of the genus Potexvirus.

DHX29 protein-coding gene in the species Homo sapiens

DExH-box helicase 29 (DHX29) is a 155 kDa protein that in humans is encoded by the DHX29 gene.

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 (October 2004). "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" (Free full text). The Journal of Biological Chemistry. 279 (44): 46253–62. doi:10.1074/jbc.M408155200. PMID   15319423.
  2. ↑ Chen J, Zhao XN, Yang L, Hu GJ, Lu M, Xiong Y, Yang XY, Chang CC, Song BL, Chang TY, Li BL (September 2008). "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. doi:10.1038/cr.2008.66. PMC   3086790 . PMID   18542101.
  3. ↑ Yang L, Chen J, Chang CC, Yang XY, Wang ZZ, Chang TY, Li BL (April 2004). "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. doi:10.1093/abbs/36.4.259. PMID   15253151. Archived from the original (Free full text) on 2016-03-03.
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