Antizyme RNA frameshifting stimulation element

Antizyme RNA frameshifting stimulation element
	Predicted secondary structure and sequence conservation of Antizyme_FSE
Identifiers
Symbol	Antizyme_FSE
Rfam	RF00381
Other data
RNA type	Cis-reg; frameshift_element
Domain(s)	Eukaryota
SO	0000233
PDB structures	PDBe

Last updated October 02, 2019

Antizyme RNA frameshifting stimulation element is a structural element which is found in antizyme mRNA and is known to promote frameshifting. Antizyme genes have two partially overlapping open reading frames, the second, which encodes the functional (antizyme) protein requires +1 translational frameshifting. This frameshift is stimulated by a pseudoknot present 3' of the frameshift site in the antizyme mRNA. The frameshifting efficiency is dependent on the concentration of polyamines in the cell, when the polyamine concentration is high frameshifting is more likely to occur which leads to an increase in the quantity of functional antizyme produced. The functional antizyme acts to reduce ornithine decarboxylase (ODC) activity which leads to a drop in polyamines present in the cell. Therefore, this family can be thought of as a biosensor for intracellular free polyamines that functions via a negative feedback loop.^[1]

Cis-regulatory elements (CREs) are regions of non-coding DNA which regulate the transcription of neighboring genes. CREs are vital components of genetic regulatory networks, which in turn control morphogenesis, the development of anatomy, and other aspects of embryonic development, studied in evolutionary developmental biology.

In molecular biology, Ornithine decarboxylase antizyme (ODC-AZ) is an ornithine decarboxylase inhibitor. It binds to, and destabilises, ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis. ODC is then rapidly degraded. It was first characterized in 1981. The expression of ODC-AZ requires programmed, ribosomal frameshifting which is modulated according to the cellular concentration of polyamines. High levels of polyamines induce a +1 ribosomal frameshift in the translation of mRNA for the antizyme leading to the expression of a full-length protein. At least two forms of ODC-AZ exist in mammals and the protein has been found in Drosophila as well as in Saccharomyces yeast.

In molecular genetics, an open reading frame (ORF) is the part of a reading frame that has the ability to be translated. An ORF is a continuous stretch of codons that begins with a start codon and ends at a stop codon. An ATG codon within the ORF may indicate where translation starts. The transcription termination site is located after the ORF, beyond the translation stop codon. If transcription were to cease before the stop codon, an incomplete protein would be made during translation. In eukaryotic genes with multiple exons, introns are removed and exons are then joined together after transcription to yield the final mRNA for protein translation. In the context of gene finding, the start-stop definition of an ORF therefore only applies to spliced mRNAs, not genomic DNA, since introns may contain stop codons and/or cause shifts between reading frames. An alternative definition says that an ORF is a sequence that has a length divisible by three and is bounded by stop codons. This more general definition can also be useful in the context of transcriptomics and/or metagenomics, where start and/or stop codon may not be present in the obtained sequences. Such an ORF corresponds to parts of a gene rather than the complete gene.

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Coronaviridae is a family of enveloped, positive-sense, single-stranded RNA viruses. The viral genome is 26–32 kb in length. The particles are typically decorated with large (~20 nm), club- or petal-shaped surface projections, which in electron micrographs of spherical particles create an image reminiscent of the solar corona. Members of this family are thus referred to as coronaviruses.

A pseudoknot is a nucleic acid secondary structure containing at least two stem-loop structures in which half of one stem is intercalated between the two halves of another stem. The pseudoknot was first recognized in the turnip yellow mosaic virus in 1982. Pseudoknots fold into knot-shaped three-dimensional conformations but are not true topological knots.

Coronavirus 3 stem-loop II-like motif (s2m)

The Coronavirus 3' stem-loop II-like motif is a secondary structure motif identified in the 3'untranslated region (3'UTR) of astrovirus, coronavirus and equine rhinovirus genomes. Its function is unknown, but various viral 3' UTR regions have been found to play roles in viral replication and packaging.

The Coronavirus 3' UTR pseudoknot is an RNA structure found in the coronavirus genome. Coronaviruses contain 30 kb single-stranded positive-sense RNA genomes. The 3' UTR region of these coronavirus genomes contains a conserved ~55 nucleotide pseudoknot structure which is necessary for viral genome replication. The mechanism of cis-regulation is unclear, but this element is postulated to function in the plus-strand.

In molecular biology, the coronavirus frameshifting stimulation element is a conserved stem-loop of RNA found in coronaviruses that can promote ribosomal frameshifting. Such RNA molecules interact with a downstream region to form a pseudoknot structure; the region varies according to the virus but pseudoknot formation is known to stimulate frameshifting. In the classical situation, a sequence 32 nucleotides downstream of the stem is complementary to part of the loop. In other coronaviruses, however, another stem-loop structure around 150 nucleotides downstream can interact with members of this family to form kissing stem-loops and stimulate frameshifting.

The Coronavirus packaging signal is a conserved cis-regulatory element found in Coronavirus which has an important role in regulating the packaging of the viral genome into the capsid.

The coronavirus SL-III cis-acting replication element (CRE) is an RNA element that regulates defective interfering (DI) RNA replication.

HIV ribosomal frameshift signal is a ribosomal frameshift (PRF) that human immunodeficiency virus (HIV) uses to translate several different proteins from the same sequence.

Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process can be programmed by the nucleotide sequence of the mRNA and is sometimes affected by the secondary, 3-dimensional mRNA structure. It has been described mainly in viruses, retrotransposons and bacterial insertion elements, and also in some cellular genes.

Ornithine decarboxylase antizyme is an enzyme that in humans is encoded by the OAZ1 gene.

Ornithine decarboxylase antizyme 2 is an enzyme that in humans is encoded by the OAZ2 gene.

ALIL pseudoknot is an RNA element that induces frameshifting in bacteria. The expression of a minority of genes requires frameshifting to occur where the frequency of frameshifting is increased by a RNA secondary structure located on the 3' side of the shift site. This structure can be either a pseudoknot or a stem-loop and acts as a physical barrier to mRNA translocation so therefore causes ribosome pausing.

Nucleic acid structure refers to the structure of nucleic acids such as DNA and RNA. Chemically speaking, DNA and RNA are very similar. Nucleic acid structure is often divided into four different levels: primary, secondary, tertiary and quaternary.

Nucleic acid secondary structure is the basepairing interactions within a single nucleic acid polymer or between two polymers. It can be represented as a list of bases which are paired in a nucleic acid molecule. The secondary structures of biological DNA's and RNA's tend to be different: biological DNA mostly exists as fully base paired double helices, while biological RNA is single stranded and often forms complex and intricate base-pairing interactions due to its increased ability to form hydrogen bonds stemming from the extra hydroxyl group in the ribose sugar.

A polyamine is an organic compound having more than two amino groups. Alkyl polyamines occur naturally but are also synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. Most aromatic polyamines are crystalline solids at room temperature.

Ribosomal pause refers to the queueing or stacking of ribosomes during translation of the nucleotide sequence of mRNA transcripts. These transcripts are decoded and converted into amino acid sequence during protein synthesis by ribosomes. The pause sites of the mRNAs only briefly interrupt the progress of translation. Within the ribosome, transfer RNA molecules recognize specific trinucleotide codons on the mRNA, and add their cognate amino acids to nascent protein chains.

A slippery sequence is a small section of codon nucleotide sequences that controls the rate of ribosomal frameshifting. A slippery sequence causes a faster ribosomal transfer which in turn can cause the reading ribosome to "slip." This allows a tRNA to shift by 1 base after it has paired with its anticodon, changing the reading frame.

References

↑ Ivanov IP, Anderson CB, Gesteland RF, Atkins JF (2004). "Identification of a new antizyme mRNA +1 frameshifting stimulatory pseudoknot in a subset of diverse invertebrates and its apparent absence in intermediate species". J Mol Biol. 339 (3): 495–504. doi:10.1016/j.jmb.2004.03.082. PMID 15147837.

External links

Page for Antizyme RNA frameshifting stimulation element at Rfam

Rfam is a database containing information about non-coding RNA (ncRNA) families and other structured RNA elements. It is an annotated, open access database originally developed at the Wellcome Trust Sanger Institute in collaboration with Janelia Farm, and currently hosted at the European Bioinformatics Institute. Rfam is designed to be similar to the Pfam database for annotating protein families.

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[1] Ivanov IP, Anderson CB, Gesteland RF, Atkins JF (2004). "Identification of a new antizyme mRNA +1 frameshifting stimulatory pseudoknot in a subset of diverse invertebrates and its apparent absence in intermediate species". J Mol Biol. 339 (3): 495–504. doi:10.1016/j.jmb.2004.03.082. PMID 15147837.