Toxoplasma lactate dehydrogenase 1 regulatory UTR

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LDH1 5′UTR
RF02697.svg
Predicted secondary structure and sequence conservation of LDH1 5′UTR
Identifiers
Rfam RF02697
Other data
Domain(s) Bacteria
GO GO term must start with GO:
SO SO:0005836,SO:0000204
PDB structures PDBe

In Toxoplasma gondii the translational repression of lactate dehydrogenase 1 (LDH1) was discovered to be mediated through its 5′UTR. A small nucleotide regulatory RNA hairpin was shown to be essential for the repression. It is possible that this hairpin may act as the nucleation site for the binding of an trans-acting factor(s) that allow for the translational repression. [1]

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Toxoplasmosis Parasitic disease

Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii. Infections with toxoplasmosis usually cause no obvious symptoms in adults. Occasionally, people may have a few weeks or months of mild, flu-like illness such as muscle aches and tender lymph nodes. In a small number of people, eye problems may develop. In those with a weak immune system, severe symptoms such as seizures and poor coordination may occur. If infected during pregnancy, a condition known as congenital toxoplasmosis may affect the child.

<i>Toxoplasma gondii</i>

Toxoplasma gondii is an obligate intracellular parasitic protozoan eukaryote that causes the infectious disease toxoplasmosis. Found worldwide, T. gondii is capable of infecting virtually all warm-blooded animals, but felids, such as domestic cats, are the only known definitive hosts in which the parasite may undergo sexual reproduction.

A regulatory sequence is a segment of a nucleic acid molecule which is capable of increasing or decreasing the expression of specific genes within an organism. Regulation of gene expression is an essential feature of all living organisms and viruses.

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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.

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Amino acid synthesis

Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can only synthesize 11 of the 20 standard amino acids, and in time of accelerated growth, histidine can be considered an essential amino acid.

lin-4 microRNA precursor

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mir-2 microRNA precursor

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Lactate dehydrogenase

Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one molecule to another.

NrrF RNA

NrrF is a non-coding RNA which is regulated by the Ferric uptake regulator (Fur) protein in bacteria. This non-coding RNA was identified in Neisseria meningitidis and is involved in iron regulation of the succinate dehydrogenase genes sdhA and sdhC. NrrF acts as an antisense RNA and is complementary to the junction between the second and third genes of the sdh operon. Secondary structure predictions have indicated that this interaction occurs in a single stranded loop region of the NrrF RNA. Under low iron concentration NrrF is present at a high concentration and forms a duplex with the transcript in Hfq dependent manner. The RNA chaperone Hfq acts to enhance binding of NrrF or stabilizes the NrrF/sdh transcript duplex. Binding of NrrF results in down regulation of the sdhCDAB mRNA transcript results in a Fur-dependent positive regulation of succinate dehydrogenase. Another NrrF RNA target is mRNA petABC, coding for cytochrome bc1. Interaction between NrrF and the 5′ untranslated region of the petABC mRNA results in its repression.

Translational regulation refers to the control of the levels of protein synthesized from its mRNA. This regulation is vastly important to the cellular response to stressors, growth cues, and differentiation. In comparison to transcriptional regulation, it results in much more immediate cellular adjustment through direct regulation of protein concentration. The corresponding mechanisms are primarily targeted on the control of ribosome recruitment on the initiation codon, but can also involve modulation of peptide elongation, termination of protein synthesis, or ribosome biogenesis. While these general concepts are widely conserved, some of the finer details in this sort of regulation have been proven to differ between prokaryotic and eukaryotic organisms.

RNA thermometer

An RNA thermometer is a temperature-sensitive non-coding RNA molecule which regulates gene expression. RNA thermometers often regulate genes required during either a heat shock or cold shock response, but have been implicated in other regulatory roles such as in pathogenicity and starvation.

SAG1 protein domain

In molecular biology, the SAG1 protein domain is an example of a group of glycosylphosphatidylinositol (GPI)-linked proteins named SRSs. SAG1 is found on the surface of a protozoan parasite Toxoplasma gondii. This parasite infects almost any warm-blooded vertebrate. The surface of T. gondii is coated with a family of developmentally regulated glycosylphosphatidylinositol (GPI)-linked proteins (SRSs), of which SAG1 is the prototypic member.

In molecular biology mir-198 microRNA is a short RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms.

In molecular biology, the PyrC leader is a cis-regulatory RNA element found at the 5' of the PyrC mRNA in Enterobacteria. The PyrC gene encodes Dihydroorotase, an enzyme involved in pyrimidine biosynthesis. The PyrC leader regulates expression of PyrC. Translation initiation can occur at four different sites within this leader sequence, under high CTP conditions the translation initiation site is upstream of that used under low CTP conditions, additional cytosine residues are incorporated into the mRNA resulting in the formation of an RNA hairpin. This hairpin blocks ribosome-binding at the Shine-Dalgarno sequence, and therefore blocks expression of PyrC. Under low CTP conditions the initiation site is further downstream and does not result in hairpin formation, so the ribosome can bind to the Shine-Dalgarno sequence and PyrC is expressed.

In molecular biology, the PyrD leader is a cis-regulatory RNA element found at the 5' of the PyrC mRNA in Proteobacteria. The PyrD gene encodes dihydroorotate dehydrogenase, an enzyme involved in pyrimidine biosynthesis. The PyrD leader regulates expression of PyrD. Translation initiation can occur at more than one different site within this leader sequence, under high cytidine triphosphate or guanosine triphosphate conditions the translation initiation site is upstream of that used under low CTP/GTP conditions, additional cytosine residues are incorporated into the mRNA resulting in the formation of an RNA hairpin. This hairpin blocks ribosome-binding at the Shine-Dalgarno sequence, and therefore blocks expression of PyrD. Under low CTP/GTP conditions the initiation site is further downstream and does not result in hairpin formation, so the ribosome can bind to the Shine-Dalgarno sequence and PyrD is expressed.

References

  1. Holmes M, Itaas V, Ananvoranich S (November 2014). "Sustained translational repression of lactate dehydrogenase 1 in Toxoplasma gondii bradyzoites is conferred by a small regulatory RNA hairpin". The FEBS Journal. 281 (22): 5077–5091. doi:10.1111/febs.13048. PMID   25223457. S2CID   45643970.