- Volume 42 Issue 6
DOI QR Code
Heterogeneous Sequences of Brain Cytoplasmic 200 RNA Formed by Multiple Adenine Nucleotide Insertions
Shin, Heegwon;Lee, Jungmin;Kim, Youngmi;Jang, Seonghui;Kim, Meehyein;Lee, Younghoon
- Received : 2019.05.24
- Accepted : 2019.06.06
- Published : 2019.06.30
Brain cytoplasmic 200 RNA (BC200 RNA), originally identified as a neuron-specific non-coding RNA, is also observed in various cancer cells that originate from non-neural cells. Studies have revealed diverse functions of BC200 RNA in cancer cells. Accordingly, we hypothesized that BC200 RNA might be modified in cancer cells to generate cancerous BC200 RNA responsible for its cancer-specific functions. Here, we report that BC200 RNA sequences are highly heterogeneous in cancer cells by virtue of multiple adenine nucleotide insertions in the internal A-rich region. The insertion of adenine nucleotides enhances BC200 RNA-mediated translation inhibition, possibly by increasing the binding affinity of BC200 RNA for eIF4A (eukaryotic translation initiation factor 4A).
adenine nucleotide insertion;BC200 RNA;cancer cells;eIF4A;translation inhibition
- Baranov, P.V., Hammer, A.W., Zhou, J., Gesteland, R.F., and Atkins, J.F. (2005). Transcriptional slippage in bacteria: distribution in sequenced genomes and utilization in IS element gene expression. Genome Biol. 6, R25.
- Booy, E.P., McRae, E.K., Koul, A., Lin, F., and McKenna, S.A. (2017). The long non-coding RNA BC200 (BCYRN1) is critical for cancer cell survival and proliferation. Mol. Cancer 16, 109.
- Briggs, J.A., Wolvetang, E.J., Mattick, J.S., Rinn, J.L., and Barry, G. (2015). Mechanisms of long non-coding RNAs in mammalian nervous system development, plasticity, disease, and evolution. Neuron 88, 861-877.
- Chen, W., Bocker, W., Brosius, J., and Tiedge, H. (1997). Expression of neural BC200 RNA in human tumours. J. Pathol. 183, 345-351.
- Eom, T., Berardi, V., Zhong, J., Risuleo, G., and Tiedge, H. (2011). Dual nature of translational control by regulatory BC RNAs. Mol. Cell. Biol. 31, 4538-4549.
- Han, K., Kim, K.S., Bak, G., Park, H., and Lee, Y. (2010). Recognition and discrimination of target mRNAs by Sib RNAs, a cis-encoded sRNA family. Nucleic Acids Res. 38, 5851-5866.
- Hu, T. and Lu, Y.R. (2015). BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer. Cancer Cell Int. 15, 36.
- Jang, S., Shin, H., Lee, J., Kim, Y., Bak, G., and Lee, Y. (2017). Regulation of BC200 RNA-mediated translation inhibition by hnRNP E1 and E2. FEBS Lett. 591, 393-405.
- Jung, E., Lee, J., Hong, H.J., Park, I., and Lee, Y. (2014). RNA recognition by a human antibody against brain cytoplasmic 200 RNA. RNA 20, 805-814.
- Kim, Y., Lee, J., Shin, H., Jang, S., Kim, S.C., and Lee, Y. (2017). Biosynthesis of brain cytoplasmic 200 RNA. Sci. Rep. 7, 6884.
- Kondrashov, A.V., Kiefmann, M., Ebnet, K., Khanam, T., Muddashetty, R.S., and Brosius, J. (2005). Inhibitory effect of naked neural BC1 RNA or BC200 RNA on eukaryotic in vitro translation systems is reversed by poly(A)-binding protein (PABP). J. Mol. Biol. 353, 88-103. https://doi.org/10.1016/j.jmb.2005.07.049
- Larsen, B., Wills, N.M., Nelson, C., Atkins, J.F., and Gesteland, R.F. (2000). Nonlinearity in genetic decoding: homologous DNA replicase genes use alternatives of transcriptional slippage or translational frameshifting. Proc. Natl. Acad. Sci. U.S.A. 97, 1683-1688.
- Lin, D., Pestova, T.V., Hellen, C.U., and Tiedge, H. (2008). Translational control by a small RNA: dendritic BC1 RNA targets the eukaryotic initiation factor 4A helicase mechanism. Mol. Cell. Biol. 28, 3008-3019. https://doi.org/10.1128/MCB.01800-07
- Liu, X. and Gorovsky, M.A. (1993). Mapping the 5' and 3' ends of Tetrahymena thermophila mRNAs using RNA ligase mediated amplification of cDNA ends (RLM-RACE). Nucleic Acids Res. 21, 4954-4960.
- Muddashetty, R., Khanam, T., Kondrashov, A., Bundman, M., Iacoangeli, A., Kremerskothen, J., Duning, K., Barnekow, A., Huttenhofer, A., Tiedge, H., et al. (2002). Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles. J. Mol. Biol. 321, 433-445.
- Mus, E., Hof, P.R., and Tiedge, H. (2007). Dendritic BC200 RNA in aging and in Alzheimer's disease. Proc. Natl. Acad. Sci. U.S.A. 104, 10679-10684.
- Peng, J., Hou, F., Feng, J., Xu, S.X., and Meng, X.Y. (2018). Long non-coding RNA BCYRN1 promotes the proliferation and metastasis of cervical cancer via targeting microRNA-138 in vitro and in vivo. Oncol. Lett. 15, 5809-5818.
- Ren, H., Yang, X., Yang, Y., Zhang, X., Zhao, R., Wei, R., Zhang, X., and Zhang, Y. (2018). Upregulation of LncRNA BCYRN1 promotes tumor progression and enhances EpCAM expression in gastric carcinoma. Oncotarget 9, 4851-4861.
- Samson, J., Cronin, S., and Dean, K. (2018). BC200 (BCYRN1) - the shortest, long, non-coding RNA associated with cancer. Noncoding RNA Res. 3, 131-143.
- Shin, H., Kim, Y., Kim, M., and Lee, Y. (2018). BC200 RNA: an emerging therapeutic target and diagnostic marker for human cancer. Mol. Cells 41, 993-999.
- Shin, H., Lee, J., Kim, Y., Jang, S., Lee, Y., Kim, S., and Lee, Y. (2017a). Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11. RNA Biol. 14, 1418-1430.
- Shin, H., Lee, J., Kim, Y., Jang, S., Ohn, T., and Lee, Y. (2017b). Identifying the cellular location of brain cytoplasmic 200 RNA using an RNA-recognizing antibody. BMB Rep. 50, 318-322.
- Shinde, D., Lai, Y., Sun, F., and Arnheim, N. (2003). Taq DNA polymerase slippage mutation rates measured by PCR and quasi-likelihood analysis: (CA/GT)n and (A/T)n microsatellites. Nucleic Acids Res. 31, 974-980.
- Singh, R., Gupta, S.C., Peng, W.X., Zhou, N., Pochampally, R., Atfi, A., Watabe, K., Lu, Z., and Mo, Y.Y. (2016). Regulation of alternative splicing of Bcl-x by BC200 contributes to breast cancer pathogenesis. Cell Death Dis. 7, e2262.
- Tiedge, H., Chen, W., and Brosius, J. (1993). Primary structure, neural-specific expression, and dendritic location of human BC200 RNA. J. Neurosci. 13, 2382-2390.
- Watson, J.B. and Sutcliffe, J.G. (1987). Primate brain-specific cytoplasmic transcript of the Alu repeat family. Mol. Cell. Biol. 7, 3324-3327.
- Wu, J., Xie, F., Qian, K., Gibson, A.W., Edberg, J.C., and Kimberly, R.P. (2011). FAS mRNA editing in human systemic lupus erythematosus. Hum. Mutat. 32, 1268-1277.
Supported by : NRF, KRICT, KAIST