An RNA-binding-protein, NONO governs energy metabolism by regulating NAMPT in lung cancer

AbstractRNA-binding proteins are key players in coordinated post-transcriptional regulation of functionally related genes, defined as RNA regulons. RNA regulons play particularly critical roles in parasitic trypanosomes, which exhibit unregulated co-transcription of long arrays of unrelated genes. In this report, we present a systematic analysis of an essential RNA-binding protein, RBP42, in the mammalian-infective slender bloodstream form of African trypanosome, and we show that RBP42 is a key regulator of parasite’s central carbon and energy metabolism. Using individual-nucleotide resolution UV cross-linking and immunoprecipitation (iCLIP) to identify genome-wide RBP42-RNA interactions, we show that RBP42 preferentially binds within the coding region of mRNAs encoding core metabolic enzymes. Using global quantitative transcriptomic and proteomic analyses, we also show that loss of RBP42 reduces the abundance of target mRNA-encoded proteins, but not target mRNA, suggesting a plausible role of RBP42 as a positive regulator of target mRNA translation. Analysis reveals significant changes in central carbon metabolic intermediates following loss of RBP42, further supporting its critical role in cellular energy metabolism.

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hnRNPA2B1-Mediated Extracellular Vesicles Sorting of miR-122-5p Potentially Promotes Lung Cancer Progression

International Journal of Molecular Sciences ◽

10.3390/ijms222312866 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12866

Author(s):

Chuang Li ◽

Fang Qin ◽

Wei Wang ◽

Yifan Ni ◽

Mingyu Gao ◽

...

Keyword(s):

Lung Cancer ◽

Extracellular Vesicles ◽

Cancer Progression ◽

Tumor Metastasis ◽

Rna Binding ◽

Binding Protein ◽

Rna Binding Protein ◽

Small Cell ◽

Small Cell Lung ◽

Non Coding Rna

Extracellular vesicles (EVs) released by tumor cells play important roles on the remodeling of the tumor–stromal environment and on promoting tumor metastasis. Our earlier studies revealed that miR-122-5p, a type of small non-coding RNA, was dysregulated in non-small cell lung cancer (NSCLC) cell-derived EVs. In this study, we found that miR-122-5p was selectively sorted and secreted into lung cancer EVs through binding to RNA-binding protein hnRNPA2B1. In addition, we found that hnRNPA2B1 interacted with miR-122-5p through the EXO-motif. The delivering of lung cancer EVs-miR-122-5p promoted the migration of liver cells, which may play roles in establishing a pre-metastatic micro-environment and hepatic metastasis of lung cancer. Importantly, our findings revealed the molecular mechanism that RNA-binding protein controls the selective sorting of tumor-derived EV miR-122-5p, which potentially promotes lung cancer progression.

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Nuclear TARBP2 drives oncogenic dysregulation of RNA splicing and decay

10.1101/389213 ◽

2018 ◽

Author(s):

Lisa Fish ◽

Hoang C.B. Nguyen ◽

Steven Zhang ◽

Myles Hochman ◽

Brian D. Dill ◽

...

Keyword(s):

Gene Expression ◽

Lung Cancer ◽

Transcription Factor ◽

Rna Binding ◽

Binding Protein ◽

Intron Retention ◽

Rna Stability ◽

Rna Binding Protein ◽

List Type ◽

Gene Expression Control

SUMMARYPost-transcriptional regulation of RNA stability is a key step in gene expression control. We describe a regulatory program, mediated by the double-stranded RNA binding protein TARBP2, that controls RNA stability in the nucleus. TARBP2 binding to pre-mRNAs results in increased intron retention, subsequently leading to targeted degradation of TARBP2-bound transcripts. This is mediated by TARBP2 recruitment of the m6A RNA methylation machinery to its target transcripts, where deposition of m6A marks influences the recruitment of splicing regulators, inhibiting efficient splicing. Interactions between TARBP2 and the nucleoprotein TPR then promote degradation of these TARBP2-bound transcripts by the nuclear exosome. Additionally, analysis of clinical gene expression datasets revealed a functional role for this TARBP2 pathway in lung cancer. Using xenograft mouse models, we find that TARBP2 impacts tumor growth in the lung, and that this function is dependent on TARBP2-mediated destabilization of ABCA3 and FOXN3. Finally, we establish the transcription factor ZNF143 as an upstream regulator of TARBP2 expression.RESEARCH HIGHLIGHTSThe RNA-binding protein TARBP2 controls the stability of its target transcripts in the nucleusNuclear TARBP2 recruits the methyltransferase complex to deposit m6A marks on its target transcriptsTARBP2 and m6A-mediated interactions with splicing and nuclear RNA surveillance complexes result in target transcript intron retention and decay.Increased TARBP2 expression is associated with lung cancer and promotes lung cancer growthin vivo.The transcription factor ZNF143 drives oncogenic TARBP2 upregulation in lung cancer.

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