General Information of Drug Therapeutic Target (DTT) (ID: TT7V0K4)

DTT Name Ribonuclease L (RNASEL)
Synonyms Ribonuclease 4; RNase L; RNS4; 25Adependent ribonuclease; 25Adependent RNase; 2-5A-dependent ribonuclease; 2-5A-dependent RNase
Gene Name RNASEL
DTT Type
Literature-reported target
[1]
BioChemical Class
Endoribonucleases
UniProt ID
RN5A_HUMAN
TTD ID
T25200
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.1.26.-
Sequence
MESRDHNNPQEGPTSSSGRRAAVEDNHLLIKAVQNEDVDLVQQLLEGGANVNFQEEEGGW
TPLHNAVQMSREDIVELLLRHGADPVLRKKNGATPFILAAIAGSVKLLKLFLSKGADVNE
CDFYGFTAFMEAAVYGKVKALKFLYKRGANVNLRRKTKEDQERLRKGGATALMDAAEKGH
VEVLKILLDEMGADVNACDNMGRNALIHALLSSDDSDVEAITHLLLDHGADVNVRGERGK
TPLILAVEKKHLGLVQRLLEQEHIEINDTDSDGKTALLLAVELKLKKIAELLCKRGASTD
CGDLVMTARRNYDHSLVKVLLSHGAKEDFHPPAEDWKPQSSHWGAALKDLHRIYRPMIGK
LKFFIDEKYKIADTSEGGIYLGFYEKQEVAVKTFCEGSPRAQREVSCLQSSRENSHLVTF
YGSESHRGHLFVCVTLCEQTLEACLDVHRGEDVENEEDEFARNVLSSIFKAVQELHLSCG
YTHQDLQPQNILIDSKKAAHLADFDKSIKWAGDPQEVKRDLEDLGRLVLYVVKKGSISFE
DLKAQSNEEVVQLSPDEETKDLIHRLFHPGEHVRDCLSDLLGHPFFWTWESRYRTLRNVG
NESDIKTRKSESEILRLLQPGPSEHSKSFDKWTTKINECVMKKMNKFYEKRGNFYQNTVG
DLLKFIRNLGEHIDEEKHKKMKLKIGDPSLYFQKTFPDLVIYVYTKLQNTEYRKHFPQTH
SPNKPQCDGAGGASGLASPGC
Function
In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis. Might play a central role in the regulation of mRNA turnover. Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length. Endoribonuclease that functions in the interferon (IFN) antiviral response.
KEGG Pathway
NOD-like receptor signaling pathway (hsa04621 )
Hepatitis C (hsa05160 )
Influenza A (hsa05164 )
Herpes simplex virus 1 infection (hsa05168 )
Reactome Pathway
Interferon alpha/beta signaling (R-HSA-909733 )
OAS antiviral response (R-HSA-8983711 )
BioCyc Pathway
MetaCyc:HS06069-MON

References

1 Role of 2-5A-dependent RNase-L in senescence and longevity. Oncogene. 2007 May 10;26(21):3081-8.