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bioRxiv · 10.1101/2023.06.22.546166

snoRNA-guided tRNA 2'-O-methylation controls codon-biased gene expression and cellular states

Zhang, M.·Li, K.·Bai, J.·Van Damme, R.·Zhang, W.·Alba, M.·Stiles, B. L.·Chen, J.·Lu, Z.
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Abstract

snoRNAs are a large family of noncoding (nc)RNAs present across eukaryotes and archaea. While a subset of them guide 2-O- methylation (Nm) and pseudouridylation ({Psi}) of rRNAs and snRNAs, targets of most snoRNAs remain unknown. Here we used PARIS2 to map snoRNA targets, revealing an extensive and conserved snoRNA-tRNA interaction network. Using optimized denatured RiboMeth-seq (dRMS), we discovered snoRNA-guided Nm sites in ncRNAs, including tRNAs. Loss of snoRNAs and their associated 2-O-methyltransferase FBL reduced tRNA modifications and increased fragmentation. CRISPR knockout of the D97/D133 family of snoRNAs reduced the activity and levels of several target tRNAs, including elongator (e)Met-CAU, leading to codon-biased transcriptome and translatome in human cells. The codon-biased gene expression tipped the balance between the dichotomous cellular states of proliferation and differentiation, and skewed germ layer potential of mouse embryonic stem cells. Together, we discovered a snoRNA-guided tRNA modification mechanism controlling codon-biased gene expression and cellular states.

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Zhang, M., Li, K., Bai, J., Van Damme, R., Zhang, W., Alba, M., Stiles, B. L., Chen, J., Lu, Z.. 2023-06-22. snoRNA-guided tRNA 2'-O-methylation controls codon-biased gene expression and cellular states. https://doi.org/10.1101/2023.06.22.546166

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