Identifying the cellular location of brain cytoplasmic 200 RNA using an RNA-recognizing antibody

Shin, Heegwon; Lee, Jungmin; Kim, Youngmi; Jang, Seonghui; Ohn, Takbum; Lee, Younghoon

doi:10.5483/bmbrep.2017.50.6.217

Cited by 6 publications

(5 citation statements)

References 22 publications

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“…Therefore, it is possible that BC200 RNA may be distinctly localized in the cytoplasm and inhibit translation of specifically localized mRNAs. Our recent finding that BC200 RNA appears as fine punctate staining in the cytoplasm of HeLa cells 38 may support this hypothesis. Although we herein focused on S100A11 as a downstream partner, BC200 RNA seems to have various effects on cancer cells.…”

Section: Discussionmentioning

confidence: 55%

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

et al. 2017

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Although BC200 RNA is best known as a neuron-specific non-coding RNA, it is overexpressed in various cancer cells. BC200 RNA was recently shown to contribute to metastasis in several cancer cell lines, but the underlying mechanism was not understood in detail. To examine this mechanism, we knocked down BC200 RNA in cancer cells, which overexpress the RNA, and examined cell motility, profiling of ribosome footprints, and the correlation between cell motility changes and genes exhibiting altered ribosome profiles. We found that BC200 RNA knockdown reduced cell migration and invasion, suggesting that BC200 RNA promotes cell motility. Our ribosome profiling analysis identified 29 genes whose ribosomal occupations were altered more than 2-fold by BC200 RNA knockdown. Many (> 30%) of them were directly or indirectly related to cancer progression. Among them, we focused on S100A11 (which showed a reduced ribosome footprint) because its expression was previously shown to increase cellular motility. S100A11 was decreased at both the mRNA and protein levels following knockdown of BC200 RNA. An actinomycin-chase experiment showed that BC200 RNA knockdown significantly decreased the stability of the S100A11 mRNA without changing its transcription rate, suggesting that the downregulation of S100A11 was mainly caused by destabilization of its mRNA. Finally, we showed that the BC200 RNAknockdown-induced decrease in cell motility was mainly mediated by S100A11. Together, our results show that BC200 RNA promotes cell motility by stabilizing S100A11 transcripts.

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Section: Discussionmentioning

confidence: 55%

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

et al. 2017

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“…In the brain, BC200 and Bc1 RNAs are thought to regulate local translation in neuronal dendrites by repressing the function of translation initiation factors eIF4A and eIF4B (25). In human cell lines, BC200 RNA was also found to interact with different proteins to regulate alternative splicing (62), mRNA stability (45), and translation in p-bodies (63), implying that its role goes beyond the analogies drawn from studying Bc1 RNA. In the oligodendroglial MO3.13 cells, we found that BC200 KO led to alterations in steady-state protein levels that were partially recapitulated in POLR3A mutant cells, suggesting a dose-dependent effect of decreased BC200 RNA expression.…”

Section: Discussionmentioning

confidence: 99%

Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200

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et al. 2019

Journal of Biological Chemistry

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RNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small noncoding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A , encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3–HLD), characterized by deficient central nervous system myelination. Identification of the downstream effectors of pathogenic POLR3A mutations has so far been elusive. Here, we used CRISPR-Cas9 to introduce the POLR3A mutation c.2554A→G (p.M852V) into human cell lines and assessed its impact on Pol III biogenesis, nuclear import, DNA occupancy, transcription, and protein levels. Transcriptomic profiling uncovered a subset of transcripts vulnerable to Pol III hypofunction, including a global reduction in tRNA levels. The brain cytoplasmic BC200 RNA ( BCYRN1 ), involved in translation regulation, was consistently affected in all our cellular models, including patient-derived fibroblasts. Genomic BC200 deletion in an oligodendroglial cell line led to major transcriptomic and proteomic changes, having a larger impact than those of POLR3A mutations. Upon differentiation, mRNA levels of the MBP gene, encoding myelin basic protein, were significantly decreased in POLR3A -mutant cells. Our findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3–HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease.

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“…The internal A-rich domain of BC200 RNA is a functionally important region involved in interaction with heterogeneous nuclear ribonucleoproteins (hnRNP) E1/E2, PABP, and eIF4A ( Jang et al, 2017 ; Kondrashov et al, 2005 ). These interactions are closely related to the intracellular function and distribution of BC200 RNA ( Eom et al, 2011 ; Shin et al, 2017b ). We examined whether the length of the stretch of adenine residues affects the function of BC200 RNA.…”

Section: Resultsmentioning

confidence: 99%

Heterogeneous Sequences of Brain Cytoplasmic 200 RNA Formed by Multiple Adenine Nucleotide Insertions

Shin

Lee

Kim

et al. 2019

Molecules and Cells

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Identifying the cellular location of brain cytoplasmic 200 RNA using an RNA-recognizing antibody

Cited by 6 publications

References 22 publications

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

Leukodystrophy-associated POLR3A mutations down-regulate the RNA polymerase III transcript and important regulatory RNA BC200

Heterogeneous Sequences of Brain Cytoplasmic 200 RNA Formed by Multiple Adenine Nucleotide Insertions

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