Human DIMT1 generates N26,6A-dimethylation–containing small RNAs
| Autor: | Hui Shen, Yulia Gonskikh, Kathy Fange Liu, Julian Stoute |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
nt
nucleotide Small RNA Mutation Missense Ribosome biogenesis Biochemistry Methylation Ribosome assembly DIMT1 CHX cycloheximide Gene expression Protein biosynthesis Humans small RNA Viability assay RNA Neoplasm HEK 293T human embryonic kidney 293T cells RNA Processing Post-Transcriptional Molecular Biology AML acute myeloid leukemia Chemistry Myeloid leukemia RNA Cell Biology Methyltransferases Cell biology Neoplasm Proteins 18S rRNA Leukemia Myeloid Acute HEK293 Cells Amino Acid Substitution DIMT1 dimethyladenosine transferase 1 HPG homopropargylglycine RNA methylation PBST PBS with Tween-20 ribosome assembly poly(A)-RNA polyadenylation RNA Research Article catalytic role HA hemagglutinin |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 1083-351X 0021-9258 |
| Popis: | Dimethyladenosine transferase 1 (DIMT1) is an evolutionarily conserved RNA N6,6-dimethyladenosine (m26,6A) methyltransferase. DIMT1 plays an important role in ribosome biogenesis, and the catalytic activity of DIMT1 is indispensable for cell viability and protein synthesis. A few RNA-modifying enzymes can install the same modification in multiple RNA species. However, whether DIMT1 can work on RNA species other than 18S rRNA is unclear. Here, we describe that DIMT1 generates m26,6A not only in 18S rRNA but also in small RNAs. In addition, m26,6A in small RNAs were significantly decreased in cells expressing catalytically inactive DIMT1 variants (E85A or NLPY variants) compared with cells expressing wildtype DIMT1. Both E85A and NLPY DIMT1 variant cells present decreased protein synthesis and cell viability. Furthermore, we observed that DIMT1 is highly expressed in human cancers, including acute myeloid leukemia. Our data suggest that downregulation of DIMT1 in acute myeloid leukemia cells leads to a decreased m26,6A level in small RNAs. Together, these data suggest that DIMT1 not only installs m26,6A in 18S rRNA but also generates m26,6A-containing small RNAs, both of which potentially contribute to the impact of DIMT1 on cell viability and gene expression. |
| Databáze: | OpenAIRE |
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