RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms. Here, we demonstrate that DROSHA interacts with β-Catenin to transactivate STC1 in an RNA cleavage-independent manner, contributing to breast cancer stem-like cell (BCSC) properties. DROSHA mRNA stability is enhanced by N-methyladenosine (mA) modification which is activated by AURKA in BCSCs. AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation. Moreover, binding of AURKA to DROSHA transcript further strengthens the binding of the mA reader IGF2BP2 to stabilize mA-modified DROSHA. In addition, wild-type DROSHA, but not an mA methylation-deficient mutant, enhances BCSC stemness maintenance, while inhibition of DROSHA mA modification attenuates BCSC traits. Our study unveils the AURKA-induced oncogenic mA modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027457 | PMC |
| http://dx.doi.org/10.1038/s41422-020-00397-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genetics architecture of spontaneous coronary artery dissection in an Italian cohort.
Front Cardiovasc Med
November 2024
Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
Spontaneous coronary artery dissection (SCAD) is a relevant non-atherosclerotic cause of acute coronary syndrome with a complex genetic architecture. Recent discoveries have highlighted the potential role of miRNAs and protein-coding genes involved in the processing of small RNAs in the pathogenesis of SCAD. Furthermore, there may be a connection between SCAD and the increased cardiovascular risk observed in fragile X premutation carriers as well as a correlation with pathogenetic variants in genes encoding for collagen and extracellular matrix, which are related to connective tissue disorders (CTDs).
View Article and Find Full Text PDFMicroRNA and Rare Human Diseases.
Genes (Basel)
September 2024
Billy Blue College of Design, Torrens University Australia, Adelaide, SA 5000, Australia.
Article Synopsis
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by silencing target mRNAs and play a role in the development of rare genetic disorders.
- Dysregulation of miRNAs is linked to several Mendelian disorders, such as DICER1 syndrome and neurodevelopmental disorders, with specific examples including hearing loss and skeletal dysplasia.
- Understanding how miRNA processing abnormalities contribute to these genetic conditions is essential for diagnosis and potential therapeutic approaches.
AGO2 protein: a key enzyme in the miRNA pathway as a novel biomarker in adrenocortical carcinoma.
Endocr Relat Cancer
December 2024
School of Biomedical Engineering, University of Technology Sydney, Sydney, New South Wales, Australia.
Article Synopsis
- - Adrenocortical carcinoma (ACC) is a rare, aggressive cancer with complicated diagnosis, high recurrence rates, and poor prognosis, prompting research into potential biomarkers.
- - The study focused on miRNA processing genes, analyzing expression levels using data from TCGA and GTEx, finding that AGO2 was significantly overexpressed in ACC compared to normal and benign tissues.
- - Higher levels of AGO2 correlated with worse overall survival in ACC patients, establishing it as a promising diagnostic and prognostic biomarker for this cancer type.
The Effect of Alternative Splicing Sites on Mirtron Formation and Arm Selection of Precursor microRNAs.
Int J Mol Sci
July 2024
Gene Regulation Research Group, Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, 1117 Budapest, Hungary.
Mirtrons represent a subclass of microRNAs (miRNAs) that rely on the splicing machinery for their maturation. However, the molecular details of this Drosha-independent processing are still not fully understood; as an example, the Microprocessor complex cannot process the mirtronic pre-miRNA from the transcript even if splice site mutations are present. To investigate the influence of alternative splicing sites on mirtron formation, we generated Enhanced Green Fluorescent Protein (EGFP) reporters containing artificial introns to compare the processing of canonical miRNAs and mirtrons.
View Article and Find Full Text PDFSAFB regulates hippocampal stem cell fate by targeting Drosha to destabilize mRNA.
Elife
May 2024
Department of Biomedicine, University of Basel, Basel, Switzerland.
Neural stem cells (NSCs) are multipotent and correct fate determination is crucial to guarantee brain formation and homeostasis. How NSCs are instructed to generate neuronal or glial progeny is not well understood. Here, we addressed how murine adult hippocampal NSC fate is regulated and described how scaffold attachment factor B (SAFB) blocks oligodendrocyte production to enable neuron generation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!