Back to Search
Start Over
miRNA-mediated loss of m6A increases nascent translation in glioblastoma.
- Source :
-
PLoS genetics [PLoS Genet] 2021 Mar 08; Vol. 17 (3), pp. e1009086. Date of Electronic Publication: 2021 Mar 08 (Print Publication: 2021). - Publication Year :
- 2021
-
Abstract
- Within the glioblastoma cellular niche, glioma stem cells (GSCs) can give rise to differentiated glioma cells (DGCs) and, when necessary, DGCs can reciprocally give rise to GSCs to maintain the cellular equilibrium necessary for optimal tumor growth. Here, using ribosome profiling, transcriptome and m6A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m6A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m6A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m6A, formation of FTO/AGO1/ILF3/miR-145 complexes on a clinically relevant tumor suppressor gene (CLIP3) and significant increase in its nascent translation. Inhibition of miR-145 maintains RRACH m6A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m6A demethylation and induction of protein translation during GSC state transition.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- 3' Untranslated Regions
Adenosine metabolism
Base Sequence
Cell Line, Tumor
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Glioblastoma metabolism
Humans
Methylation
Microtubule-Associated Proteins genetics
RNA Interference
RNA, Messenger genetics
Transcriptome
Tumor Cells, Cultured
Adenosine analogs & derivatives
Glioblastoma genetics
MicroRNAs genetics
MicroRNAs metabolism
Protein Biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 17
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 33684100
- Full Text :
- https://doi.org/10.1371/journal.pgen.1009086