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FLASH GENE
Symbol RNASEL contributors: mct/npt - updated : 17-01-2017
HGNC name ribonuclease L (2',5'-oligoisoadenylate synthetase-dependent)
HGNC id 10050
Location 1q25.3      Physical location : 182.542.771 - 182.556.108
Synonym name
  • ribonuclease 4
  • 2-5A-dependent ribonuclease
  • interferon-induced 2-5A-dependent RNase
  • prostate cancer 1
  • ribonuclease 4
    • Synonym symbol(s) OIADR, RNS4, PRCA1, RN5A, HPC1, MGC133329, MGC104972, RNASE-L, DKFZp781D08126, (OAS)/RNase L
    EC.number 3.1.26.-, 3.1.27.-
    DNA
    TYPE functioning gene
    STRUCTURE 13.33 kb     6 Exon(s)
    Genomic sequence alignment details
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 4166 - 741 - 2009 19853919
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   highly
    Endocrineadrenal gland   highly
     parathyroid   highly
    Lymphoid/Immunelymph node   highly
    Nervousnervespinal nervesciatic  
    Reproductivemale systemprostate  moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • eight cysteine, histidine and lysine residues
  • nine ankyrin repeats
  • tyrosine kinase catalytic domain
    • mono polymer homomer , monomer , dimer
    HOMOLOGY
    interspecies homolog to murine Rnasel
    Homologene
    FAMILY
  • protein kinase superfamily
    • CATEGORY enzyme , immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • ribonuclease L, 2', 5'-oligoisoadenylate dependent, interferon regulated pathway, playing a role in mediating resistance to virus infection and apoptosis
  • plays an important role in the antiviral and antiproliferative activities of IFN and contributes to innate immunity and cell metabolism (Bisbal 2007)
  • key enzyme in the interferon induced antiviral and anti-proliferate pathway (Madsen 2008)
  • intracellular enzyme that is vital in innate immunity, but also is a tumor suppressor candidate (Al Ahmadi 2009)
  • RNASEL is an essential regulator of adipogenesis via the regulation of DDIT3 mRNA
  • novel function of RNASEL as an inducer of autophagy that affects viral yields
  • novel role of RNASEL in inducing autophagy affecting the outcomes of viral pathogenesis
  • regulates the expression of certain inflammatory genes
  • contributes to innate immunity through regulating macrophage functions
  • is closely connected with the pathogenesis and development of esophageal carcinoma, which act through the cellular pathways of RNASEL
  • RNA cleavage events catalyzed by RNASEL are required for optimal inflammasome activation during viral infections
  • is an antiviral endonuclease activated in virus-infected cells and cleaving viral and cellular single-stranded RNAs to produce small double-stranded RNAs with roles in amplifying host responses
  • is a regulated endoribonuclease that functions in the interferon antiviral response
  • is a negative regulator of cell migration
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimer with ABCE1, ABCE1 protein inhibits the IFN-depended RNASEL system and regulates a broad range of biological functions including viral infection, tumor cell proliferation, and antiapoptosis
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction between the androgen receptor and RNASEL mediates a cross-talk between the interferon and androgen signaling pathways
  • DDIT3 is a specific RNASEL target
  • IFN regulation by RNASEL is suggested to contribute to tissue protection and survival during viral infections
  • tristetraprolin (TTP) and RNASEL proteins interacted in cells suggesting that RNASEL is directed to cleave TTP-bound RNAs as a mechanism of substrate specificity
  • interaction between the antiviral endoribonuclease RNASEL and the actin-binding protein FLNA that enhances host defense by preventing viral entry into naive cells
  • can bind to several cytoskeletal proteins, including FLNA, an actin-binding protein that collaborates with RNASEL to maintain the cellular barrier to viral entry
  • interaction of RNASEL with the E3 ubiquitin ligase and scaffolding protein LNX1, a regulator of tight junction proteins
  • RNASEL inhibitor, ABCE1 is currently recognized as an essential translation factor involved in several stages of eukaryotic translation and ribosome biogenesis
    • cell & other
    REGULATION
    activated by the binding of unusual oligoadenylates (2-5A) and acts as the effector enzyme of the 2-5A system, an interferon-induced anti-virus mechanism
    induced by interferon
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral germinal mutation      
    in prostate cancer
    tumoral       loss of function
    by somatic mutations in rare prostatic cancer
    constitutional     --over  
    decreases cellular growth and inhibits the RNA-binding protein, ELAVL1, a regulator of cell-cycle progression and tumorigenesis (El-Ahmadi 2009)
    constitutional germinal mutation      
    that may play a role in regulating HDLc levels '
    Susceptibility
  • to prostate cancer (familial form), minor role
  • to sporadic and familial pancreatic cancer
  • to head and neck, uterine cervix and breast cancer
    • Variant & Polymorphism SNP , other
  • Arg 462 GLN associated with familial prostate cancer
  • variants Glu265X and Arg462Gln may contribute to the tumorigenesis of sporadic and familial pancreatic cancer
  • SNP rs3738579 predicts increased risk of head and neck, uterine cervix and breast cancer (Madsen 2008)
  • variants in RNASEL had the strongest effects on prostate cancer risk estimates in Hispanics and also showed an interaction effect of family history (Beuten 2010)
  • three RNASEL variants that are associated with risk for prostate cancer
    • Candidate gene general marker for cancer risk and not restricted to familial prostate cancer (Madsen 2008)
    Marker
    Therapy target
    ANIMAL & CELL MODELS