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- Table of Contents
Facts about 2-5A-dependent ribonuclease.
RNASEL mediated apoptosis is caused by a JNK-dependent stress- response pathway resulting in cytochrome c release from mitochondria and caspase-dependent apoptosis. Consequently, activation of RNASEL could lead to elimination of virus infected cells under some circumstances.
Human | |
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Gene Name: | RNASEL |
Uniprot: | Q05823 |
Entrez: | 6041 |
Belongs to: |
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protein kinase superfamily |
2-5A-dependent ribonuclease; 2-5A-dependent RNase; 2'-5'-oligoisoadenylate synthetase-dependent; EC 3.1.26.-; HPC1; interferon-induced 2-5A-dependent RNase; MGC104972; MGC133329; PRCA1; prostate cancer 1; Ribonuclease 4; ribonuclease L (2'-5'-oligoisoadenylate synthetase-dependent); Ribonuclease L; RNase L; RNS4DKFZp781D08126
Mass (kDA):
83.533 kDA
Human | |
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Location: | 1q25.3 |
Sequence: | 1; NC_000001.11 (182573634..182589285, complement) |
Highly expressed in spleen and thymus followed by prostate, testis, uterus, small intestine, colon and peripheral blood leukocytes.
Cytoplasm. Mitochondrion.
If you're new to RNASEL testing, you may be wondering about its application. RNASEL is a component of the interferon-regulated 2-5A system and functions in both antiviral and antiproliferative roles. This article will describe the uses of RNASEL in the detection of interferon-induced interferons and viruses. To learn more about this enzyme, keep reading.
RNASEL is an enzyme with multiple antiviral and proliferative roles. Various polymorphisms have been identified in RNASEL gene. Some of them have been associated with susceptibility to HIV infections, human retroviruses, and hepatitis viruses. However, the exact role of RNASEL in human disease is still unclear.
In a study on Finnish families, a genetic variant called arg462Q was found to be associated with HPC. However, it did not explain the segregation pattern of disease among affected family members. Nevertheless, RNASEL variants were significantly enriched in families with more than two members. The study also revealed that the mutations were associated with the age at which the disease was diagnosed. This finding points to a potential modifying role for RNASEL in cancer predisposition.
In the same study, Lin et al. investigated a lung cell line from human to test the antiviral role of RNASEL. They found that RNASEL blocked replication of the Dengue virus. Alternative splicing of four human OAS genes led to 10 different isoforms, of which only p42 and p46 inhibited dengue virus replication.
RNASEL is a gene that plays a pivotal role in PCa. ELAC2, MSR1, and RNASEL are two enzymes that show different expression patterns in tumors and normal tissue. These mutations have been associated with physical inactivity, exposure to toxic agents, and processed foods. So, the genes that affect PCa are also affected by these factors.
Recent studies have suggested that RNASEL is implicated in the development of cervical cancer and that it is an important regulator of the cell cycle. TP53, which is mutated in the majority of human cancers, is a key gene for cancer. RNASEL has an important role in antiviral and apoptotic responses. The researchers also analyzed polymorphisms in RNASEL gene using pyrosequencing technology. Statistical tests were conducted to determine the association between polymorphisms and cervical cancer risk. Molecular dynamics and multifactor dimension reduction were used to identify possible gene-gene interactions.
Although RNaseL has a direct antiviral role, its effector RNASEL has been implicated in the homeostatic response to unfolded proteins in the ER. Moreover, RNASEL has a potential to act as a tumor suppressor. Furthermore, RNASEL has been implicated in apoptotic response in a variety of diseases, including cervical cancer.
The interferon-regulated 2-5A system is composed of two proteins, RNASEL and RNase-L. Both proteins are activated in response to IFN and regulate bulk protein synthesis. When the interferon is activated, the 2-5A system silences bulk protein synthesis, causing the infected cells to undergo apoptosis.
The RNASEL gene is expressed at low levels in cells but is upregulated by type I interferons. The gene is transcribed in the nucleus as an inactive monomer and accumulates in the cell cytoplasm. Upon activation of the enzyme by type I interferons, the gene produces a protein that activates constitutively expressed inactive ribonuclease L.
The IFN-regulated 2-5A system is involved in the innate immune response. It is the first line of defense against viral infection. Only a few of the genes induced by IFNs have been associated with direct antiviral activity in the cell. Other examples are the ISG15, which is an IFN-stimulated protein of 15 kDa. The Mx proteins, on the other hand, are resistance proteins to myxovirus infections.
Moreover, it appears that the activity of 2-5A is not localized. The NLS-V6 and NES-V6 produced nearly identical luminescence profiles, and they were both located in the nucleus. In addition, they were distributed evenly between the nucleus and the cytosol. In summary, these data indicate that RNASEL is a component of the interferon-regulated 2-5A system.
The RNASEL proteins also inhibit the activity of PKR, which is a key component of the interferon-regulated 2/5A system. Furthermore, the action of RNASEL is sufficient for translation arrest in cells. However, the effects of 2-5A on translation depend on PKR activity. Activated PKRs prevent translation of stress proteins.
The researchers performed qRT-PCR to determine the expression of RNASEL in different cell types. RNASEL showed increased expression in BMMs, which were enriched in Oas1a and Oas2 mRNAs. The levels of RNASEL in p-Macs were also elevated. These data suggested that RNASEL could detect interferon-induced interferons in a manner comparable to a traditional assay.
Interferons are cytokines that play an important role in the immune response. They inhibit the replication of viruses and are produced by the immune system in response to a virulent infection. They are also used therapeutically, with the most famous example being treatment for hepatitis C virus infection. Besides blocking the replication of viruses, IFNs are also used to treat multiple sclerosis and various malignancies.
Interferons are cytokines produced by cells after being exposed to a foreign agent or internal damage. They activate transcriptional programs in the surrounding tissues, triggering an innate immune response. However, IFN production requires protein synthesis. Inhibition of protein synthesis occurs because double-stranded RNA induces translational arrest in the cell. This inhibition of protein synthesis is due to signaling from conserved small RNAs.
The protein ISG15 is a 15-kDa ubiquitin homologue that controls the IFN response. The ubiquitin-specific protease 18 regulates ISG15. The researchers report that this protein is a part of IFN-induced interferons. The results from the RNASEL assay are useful in understanding the underlying mechanisms of interferon-induced inflammatory responses.
The immune response to viral infections involves all arms of the immune system. These arms are known as innate immunity and are responsible for the recognition and initiation of protective immune responses against viral infections. The innate immune response is the first line of defense against infection, and is triggered by damage-associated molecular patterns such as viral RNA and Toll-like receptors or cytoplasmic DNA sensors.
PMID: 7680958 by Zhou A., et al. Expression cloning of 2-5A-dependent RNAase: a uniquely regulated mediator of interferon action.
PMID: 11063255 by Zhou A., et al. Analysis and origins of the human and mouse RNase L genes: mediators of interferon action.