GSE197276 Identification of an RNA-binding region in 18S dimethyladenosine methyltransferase DIMT1 essential for proliferation of acute myeloid leukemia cells

Contributors : Kathy F Liu ; Julian Stoute ; Yulia Gonskikh ; Hui ShenSeries Type : Expression profiling by high throughput sequencing ; OtherOrganism : Homo sapiensAberrant assembly and function of ribosomes are implicated in cancers, including acute myeloid leukemia (AML). Here, we find that 18S rRNA methyltransferase DIMT1 is essential for AML proliferation through a non-catalytic function. We demonstrate that a positively charged cleft on DIMT1 plays an important role in RNA binding. Mutations at the identified cleft (5mutA-DIMT1) significantly weakens binding of DIMT1 to rRNA in vitro and in cells. Strikingly, the RNA-binding deficient 5mutA-DIMT1 is predominantly located in the nucleoplasm, in contrast with the primarily nucleolar localization of wild-type DIMT1. Furthermore, we demonstrate that rRNA binding is required for DIMT1 to undergo liquid-liquid phase separation in vitro, which likely promotes DIMT1 ’s nucleolar localization and its role in rRNA processing in cells. Importantly, re-expression of wild-type but not 5mutA-DIMT1 supports AML proliferation in competition-based cell proliferation assays. These results highlight the importance of targeting the catalytically independent RNA-binding a ctivity of DIMT1 for therapy of AML.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Other Homo sapiens Source Type: research