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Journal article
miRNA-mediated loss of m(6)A increases nascent translation in glioblastoma
PLoS genetics, v 17(3)
01 Mar 2021
PMID: 33684100
Featured in Collection : UN Sustainable Development Goals @ Drexel
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 m(6)A RNA sequencing, we show that GSCs from patients with different subtypes of glioblastoma share a set of transcripts, which exhibit a pattern of m(6)A loss and increased protein translation during differentiation. The target sequences of a group of miRNAs overlap the canonical RRACH m(6)A motifs of these transcripts, many of which confer a survival advantage in glioblastoma. Ectopic expression of the RRACH-binding miR-145 induces loss of m(6)A, 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 m(6)A levels of CLIP3 and inhibits its nascent translation. This study highlights a critical role of miRNAs in assembling complexes for m(6)A demethylation and induction of protein translation during GSC state transition.
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Details
- Title
- miRNA-mediated loss of m(6)A increases nascent translation in glioblastoma
- Creators
- John P. Zepecki - Rhode Island HospitalDavid Karambizi - Rhode Island HospitalJ. Eduardo Fajardo - Albert Einstein College of MedicineKristin M. Snyder - University of Minnesota, College of Veterinary Medicine, St Paul, Minnesota, United States of AmericaCharlotte Guetta-Terrier - Rhode Island HospitalOliver Y. Tang - Rhode Island HospitalJia-Shu Chen - Rhode Island HospitalAtom Sarkar - Drexel UniversityAndras Fiser - Albert Einstein College of MedicineSteven A. Toms - Brown UniversityNikos Tapinos - Rhode Island Hospital
- Publication Details
- PLoS genetics, v 17(3)
- Publisher
- Public Library Science
- Number of pages
- 25
- Grant note
- R21CA235415 / National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Warren Alpert Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurology
- Web of Science ID
- WOS:000627195900003
- Scopus ID
- 2-s2.0-85102650186
- Other Identifier
- 991019168217904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity