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強化子RNA

维基百科，自由的百科全书
強化子RNA可能的作用機制

強化子RNA（Enhancer RNA，簡稱eRNA）是真核生物基因組中強化子序列轉錄產生的非編碼RNA[1]，長50nt至4000nt之間，此類RNA於2010年由RNA測序與ChIP-seq等大規模測序技術測得[2]。強化子為基因組中與RNA聚合酶Ⅱ、中介體和轉錄因子結合以啟動基因轉錄的重要序列，其轉錄生成的強化子RNA大多留在細胞核中，此類RNA大多不穩定，易被細胞核中的外切體降解，但可能可調控其他基因的轉錄[3]。並非所有強化子皆可轉錄，有研究顯示僅有少數強化子可轉錄產生出eRNA[4]，可能為較為活躍的強化子[5]。有些強化子RNA具複雜的次級結構，並帶有m6A等鹼基修飾[5]。

強化子RNA可分為1D eRNA與2D eRNA兩大類，兩者長度、多腺苷酸化情況與轉錄方向皆有差異[6]，1D eRNA的轉錄為單向，長度可達數千nt，較常被多腺苷酸化[5]，一般由H3K4me1（英语：H3K4me1）/H3K4me3（英语：H3K4me3）比值較低的強化子轉錄[7]；2D eRNA的轉錄則為雙向，且長度較短，介於50nt至2000nt之間，轉錄的強化子H3K4me1/H3K4me3較高[8]。

有研究認為強化子RNA僅是基因轉錄的中的雜訊，即由染色體結構疏鬆的區域所隨機轉錄產生、不具重要功能的RNA[4][9][10]，但有許多研究認為強化子RNA可能具重要的轉錄調控功能，可影響特定基因的表現，其詳細機制尚不明朗，但目前已有數個假說被提出[6]，有些強化子RNA可能可和組蛋白修飾酶或轉錄因子等調控蛋白結合，以促進該強化子所控制基因的轉錄，例如周期蛋白D1基因強化子轉錄出的eRNA可結合組蛋白乙醯轉移酶以促進周期蛋白D1的轉錄[3]，受p53調控的各目標基因之強化子p53BER也可轉錄出eRNA以促進各目標基因轉錄[11]；還有些強化子RNA可能可調控其他較遠位點的基因的轉錄[12]。有eRNA可能可作為一些癌症病理狀況的生物標記[5][13]。

參考文獻

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  1. ^ Fedoseeva DM, Kretova OV, Tchurikov NA. Molecular analysis of enhancer RNAs and chromatin modifications in the region of their synthesis in Drosophila cells possessing genetic constructs. Doklady. Biochemistry and Biophysics. 2012, 442: 7–11. PMID 22419084. doi:10.1134/S1607672912010012. 
  2. ^ Kim TK, Hemberg M, Gray JM, Costa AM, Bear DM, Wu J, Harmin DA, Laptewicz M, Barbara-Haley K, Kuersten S, Markenscoff-Papadimitriou E, Kuhl D, Bito H, Worley PF, Kreiman G, Greenberg ME. Widespread transcription at neuronal activity-regulated enhancers. Nature. May 2010, 465 (7295): 182–7. PMC 3020079 可免费查阅. PMID 20393465. doi:10.1038/nature09033. 
  3. ^ 3.0 3.1 Wang X, Arai S, Song X, Reichart D, Du K, Pascual G, Tempst P, Rosenfeld MG, Glass CK, Kurokawa R. Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature. July 2008, 454 (7200): 126–30. PMC 2823488 可免费查阅. PMID 18509338. doi:10.1038/nature06992. 
  4. ^ 4.0 4.1 De Santa F, Barozzi I, Mietton F, Ghisletti S, Polletti S, Tusi BK, Muller H, Ragoussis J, Wei CL, Natoli G. Mattick JS , 编. A large fraction of extragenic RNA pol II transcription sites overlap enhancers. PLoS Biology. May 2010, 8 (5): e1000384. PMC 2867938 可免费查阅. PMID 20485488. doi:10.1371/journal.pbio.1000384. 
  5. ^ 5.0 5.1 5.2 5.3 Arnold PR, Wells AD, Li XC. Diversity and Emerging Roles of Enhancer RNA in Regulation of Gene Expression and Cell Fate.. Front Cell Dev Biol. 2019, 7: 377. PMC 6971116 可免费查阅. PMID 31993419. doi:10.3389/fcell.2019.00377. 
  6. ^ 6.0 6.1 Natoli G, Andrau JC. Noncoding transcription at enhancers: general principles and functional models. Annual Review of Genetics. 2012, 46: 1–19. PMID 22905871. doi:10.1146/annurev-genet-110711-155459. 
  7. ^ Koch F, Fenouil R, Gut M, Cauchy P, Albert TK, Zacarias-Cabeza J, Spicuglia S, de la Chapelle AL, Heidemann M, Hintermair C, Eick D, Gut I, Ferrier P, Andrau JC. Transcription initiation platforms and GTF recruitment at tissue-specific enhancers and promoters. Nature Structural & Molecular Biology. July 2011, 18 (8): 956–63. PMID 21765417. doi:10.1038/nsmb.2085. 
  8. ^ Wang D, Garcia-Bassets I, Benner C, Li W, Su X, Zhou Y, Qiu J, Liu W, Kaikkonen MU, Ohgi KA, Glass CK, Rosenfeld MG, Fu XD. Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA. Nature. May 2011, 474 (7351): 390–4. PMC 3117022 可免费查阅. PMID 21572438. doi:10.1038/nature10006. 
  9. ^ Ren B. Transcription: Enhancers make non-coding RNA. Nature. May 2010, 465 (7295): 173–4. PMID 20463730. doi:10.1038/465173a. 
  10. ^ Obrdlik A, Kukalev A, Louvet E, Farrants AK, Caputo L, Percipalle P. The histone acetyltransferase PCAF associates with actin and hnRNP U for RNA polymerase II transcription. Molecular and Cellular Biology. October 2008, 28 (20): 6342–57. PMC 2577438 可免费查阅. PMID 18710935. doi:10.1128/MCB.00766-08. 
  11. ^ Melo CA, Drost J, Wijchers PJ, van de Werken H, de Wit E, Oude Vrielink JA; et al. eRNAs are required for p53-dependent enhancer activity and gene transcription.. Mol Cell. 2013, 49 (3): 524–35. PMID 23273978. doi:10.1016/j.molcel.2012.11.021. 
  12. ^ Feng J, Bi C, Clark BS, Mady R, Shah P, Kohtz JD. The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. Genes & Development. June 2006, 20 (11): 1470–84. PMC 1475760 可免费查阅. PMID 16705037. doi:10.1101/gad.1416106. 
  13. ^ Gu X, Wang L, Boldrup L, Coates PJ, Fahraeus R, Sgaramella N; et al. AP001056.1, A Prognosis-Related Enhancer RNA in Squamous Cell Carcinoma of the Head and Neck.. Cancers (Basel). 2019, 11 (3). PMC 6468641 可免费查阅. PMID 30862109. doi:10.3390/cancers11030347. 
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