Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0019163 (
hepatitis B
)
38,309
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
N
6
-Methyladenosine (m
6
A), the methylation of the adenosine base at the nitrogen 6 position, is the most common epitranscriptomic modification of mRNA that affects a wide variety of biological functions. We have previously reported that
hepatitis B
viral RNAs are m
6
A-modified, displaying a dual functional role in the viral life cycle. Here, we show that cellular m
6
A machinery regulates host innate immunity against
hepatitis B
and C viral infections by inducing m
6
A modification of viral transcripts. The depletion of the m
6
A writer enzymes (METTL3 and METTL14) leads to an increase in viral RNA recognition by retinoic acid-inducible gene I (RIG-I), thereby stimulating type I interferon production. This is reversed in cells in which m
6
A METTL3 and METTL14 are overexpressed. The m
6
A modification of viral RNAs renders RIG-I signaling less effective, whereas single nucleotide mutation of m
6
A consensus motif of viral RNAs enhances RIG-I sensing activity. Importantly, m
6
A reader proteins (YTHDF2 and
YTHDF3
) inhibit RIG-I-transduced signaling activated by viral RNAs by occupying m
6
A-modified RNAs and inhibiting RIG-I recognition. Collectively, our results provide new insights into the mechanism of immune evasion via m
6
A modification of viral RNAs.
...
PMID:
N
6
-Methyladenosine modification of hepatitis B and C viral RNAs attenuates host innate immunity via RIG-I signaling. 3271 95
