BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

Functional analysis of RNA motifs essential for BC200 RNA-mediated translational regulation

  • 투고 : 2019.06.04
  • 심사 : 2019.06.13
  • 발행 : 2020.02.29
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Brain cytoplasmic 200 RNA (BC200 RNA) is proposed to act as a local translational modulator by inhibiting translation after being targeted to neuronal dendrites. However, the mechanism by which BC200 RNA inhibits translation is not fully understood. Although a detailed functional analysis of RNA motifs is essential for understanding the BC200 RNA-mediated translation-inhibition mechanism, there is little relevant research on the subject. Here, we performed a systematic domain-dissection analysis of BC200 RNA to identify functional RNA motifs responsible for its translational-inhibition activity. Various RNA variants were assayed for their ability to inhibit translation of luciferase mRNA in vitro. We found that the 111-200-nucleotide region consisting of part of the Alu domain as well as the A/C-rich domain (consisting of both the A-rich and C-rich domains) is most effective for translation inhibition. Surprisingly, we also found that individual A-rich, A/C-rich, and Alu domains can enhance translation but at different levels for each domain, and that these enhancing effects manifest as cap-dependent translation.

키워드

참고문헌

  1. Strobel EJ, Watters KE, Loughrey D and Lucks JB (2016) RNA systems biology: uniting functional discoveries and structural tools to understand global roles of RNAs. Curr Opin Biotechnol 39, 182-191 https://doi.org/10.1016/j.copbio.2016.03.019
  2. Cech TR and Steitz JA (2014) The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157, 77-94 https://doi.org/10.1016/j.cell.2014.03.008
  3. Wan Y, Kertesz M, Spitale RC, Segal E and Chang HY (2011) Understanding the transcriptome through RNA structure. Nat Rev Genet 12, 641-655 https://doi.org/10.1038/nrg3049
  4. Washietl S (2010) Sequence and structure analysis of noncoding RNAs. Methods Mol Biol 609, 285-306 https://doi.org/10.1007/978-1-60327-241-4_17
  5. Johnsson P, Lipovich L, Grander D and Morris KV (2014) Evolutionary conservation of long non-coding RNAs; sequence, structure, function. Biochim Biophys Acta 1840, 1063-1071 https://doi.org/10.1016/j.bbagen.2013.10.035
  6. DeChiara TM and Brosius J (1987) Neural BC1 RNA: cDNA clones reveal nonrepetitive sequence content. Proc Nat Acad Sci U S A 84, 2624-2628 https://doi.org/10.1073/pnas.84.9.2624
  7. 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 https://doi.org/10.1523/JNEUROSCI.13-06-02382.1993
  8. Skryabin BV, Kremerskothen J, Vassilacopoulou D et al (1998) The BC200 RNA gene and its neural expression are conserved in Anthropoidea (Primates). J Mol Evol 47, 677-685 https://doi.org/10.1007/PL00006426
  9. Vikram R, Ramachandran R and Abdul K (2014) Functional significance of long non-coding RNAs in breast cancer. Breast Cancer 21, 515-521 https://doi.org/10.1007/s12282-014-0554-y
  10. Hu T and Lu YR (2015) BCYRN1, a c-MYC-activated long non-coding RNA, regulates cell metastasis of non-small-cell lung cancer. Cancer Cell Int 15, 36 https://doi.org/10.1186/s12935-015-0183-3
  11. Kim Y, Lee J, Shin H, Jang S, Kim SC and Lee Y (2017) Biosynthesis of brain cytoplasmic 200 RNA. Sci Rep 7, 6884 https://doi.org/10.1038/s41598-017-05097-3
  12. Jung E, Lee J, Hong HJ, Park I and Lee Y (2014) RNA recognition by a human antibody against brain cytoplasmic 200 RNA. RNA 20, 805-814 https://doi.org/10.1261/rna.040899.113
  13. Zhao RH, Zhu CH, Li XK et al (2016) BC200 LncRNA a potential predictive marker of poor prognosis in esophageal squamous cell carcinoma patients. Onco Targets Ther 9, 2221-2226
  14. Wu DI, Wang T, Ren C et al (2016) Downregulation of BC200 in ovarian cancer contributes to cancer cell proliferation and chemoresistance to carboplatin. Oncol Lett 11, 1189-1194 https://doi.org/10.3892/ol.2015.3983
  15. Zhang XY, Zhang LX, Tian CJ et al (2016) LncRNAs BCYRN1 promoted the proliferation and migration of rat airway smooth muscle cells in asthma via upregulating the expression of transient receptor potential 1. Am J Transl Res 8, 3409-3418
  16. 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 https://doi.org/10.14348/molcells.2018.0425
  17. Rozhdestvensky TS, Kopylov AM, Brosius J and Huttenhofer A (2001) Neuronal BC1 RNA structure: evolutionary conversion of a tRNA(Ala) domain into an extended stem-loop structure. RNA 7, 722-730 https://doi.org/10.1017/S1355838201002485
  18. Sosinska P, Mikula-Pietrasik J and Ksiazek K (2015) The double-edged sword of long non-coding RNA: The role of human brain-specific BC200 RNA in translational control, neurodegenerative diseases, and cancer. Mutat Res Rev Mutat Res 766, 58-67 https://doi.org/10.1016/j.mrrev.2015.08.002
  19. Kremerskothen J, Zopf D, Walter P et al (1998) Heterodimer SRP9/14 is an integral part of the neural BC200 RNP in primate brain. Neurosci Lett 245, 123-126 https://doi.org/10.1016/S0304-3940(98)00215-8
  20. Lin D, Pestova TV, Hellen CU 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
  21. Muddashetty R, Khanam T, Kondrashov A et al (2002) Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles. J Mol Biol 321, 433-445 https://doi.org/10.1016/S0022-2836(02)00655-1
  22. Kahvejian A, Roy G and Sonenberg N (2001) The mRNA closed-loop model: the function of PABP and PABPinteracting proteins in mRNA translation. CSH Symp Quant Biol 66, 293-300 https://doi.org/10.1101/sqb.2001.66.293
  23. 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 https://doi.org/10.1128/MCB.05885-11
  24. Eom T, Muslimov IA, Tsokas P et al (2014) Neuronal BC RNAs cooperate with eIF4B to mediate activity-dependent translational control. J Cell Biol 207, 237-252 https://doi.org/10.1083/jcb.201401005
  25. Kondrashov AV, Kiefmann M, Ebnet K, Khanam T, Muddashetty RS 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
  26. Borman AM, Michel YM, Malnou CE and Kean KM (2002) Free poly(A) stimulates capped mRNA translation in vitro through the eIF4G-poly(A)-binding protein interaction. J Biol Chem 277, 36818-36824 https://doi.org/10.1074/jbc.M205065200
  27. Hasler J and Strub K (2006) Alu RNP and Alu RNA regulate translation initiation in vitro. Nucleic Acids Res 34, 2374-2385 https://doi.org/10.1093/nar/gkl246
  28. Rubin CM, Kimura RH and Schmid CW (2002) Selective stimulation of translational expression by Alu RNA. Nucleic Acids Res 30, 3253-3261 https://doi.org/10.1093/nar/gkf419
  29. Bovia F, Wolff N, Ryser S and Strub K (1997) The SRP9/14 subunit of the human signal recognition particle binds to a variety of Alu-like RNAs and with higher affinity than its mouse homolog. Nucleic Acids Res 25, 318-326 https://doi.org/10.1093/nar/25.2.318
  30. Shin H, Lee J, Kim Y et al (2017) Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizng mRNA for calcium-binding protein S100A11. RNA Biol 14, 1418-1430 https://doi.org/10.1080/15476286.2017.1297913
  31. Shin H, Lee J, Kim Y, Jang S, Ohn T, and Lee Y (2017) Identifying the cellular location of brain cytoplasmic 200 RNA using an RNA-recognizing antibody. BMB Rep 50, 318-332 https://doi.org/10.5483/BMBRep.2017.50.6.217
  32. 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 https://doi.org/10.1002/1873-3468.12544