Zhang et al. 2023 (PRJNA956925)

General Details

Title Human SAMD9 is a Poxvirus-Activatable Anticodon Nuclease Inhibiting Codon-Specific Protein Synthesis
Organism
Number of Samples 8
Release Date 2023/04/18 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP433210
ENA SRP433210
GEO GSE229979
BioProject PRJNA956925

Publication

Title
Authors Zhang F, Ji Q, Chaturvedi J, Morales M, Mao Y, Meng X, Dong L, Deng J, Qian SB, Xiang Y
Journal Science advances
Publication Date 2023 Jun 9
Abstract As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase that specifically cleaves phenylalanine tRNA (tRNA Phe ), resulting in codon-specific ribosomal pausing and stress signaling. While SAMD9 ACNase activity is normally latent in cells, it can be activated by poxvirus infection or rendered constitutively active by SAMD9 mutations associated with various human disorders, revealing tRNA Phe depletion as an antiviral mechanism and a pathogenic condition in SAMD9 disorders. We identified the N-terminal effector domain of SAMD9 as the ACNase, with substrate specificity primarily determined by a eukaryotic tRNA Phe -specific 2'- O -methylation at the wobble position, making virtually all eukaryotic tRNA Phe susceptible to SAMD9 cleavage. Notably, the structure and substrate specificity of SAMD9 ACNase differ from known microbial ACNases, suggesting convergent evolution of a common immune defense strategy targeting tRNAs.
PMC PMC10246899
PMID 37285440
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR24204967 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
SRR24204968 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
SRR24204969 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
SRR24204970 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
SRR24204966 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
SRR24204965 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
SRR24204964 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
SRR24204963 PRJNA956925 Homo sapiens HeLa Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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