環狀RNA(Circular RNA,簡稱circRNA)為生物細胞中的一類RNA,由線狀RNA5'端與3'端經共價結合(反向剪接)而形成[1]。有些環狀RNA可編碼蛋白質[2][3],有些則為非編碼RNA,大多數環狀RNA的功能均仍未知,過去認為環狀RNA僅是RNA剪接過程中產生的副產物,在細胞中數量不多且序列保守性低,應不具重要功能[4],但近年許多研究已漸推翻此觀點[1][5][6]。環狀RNA因不具5'端或3'端,不會被外切酶切割,在細胞中應較多數的線狀RNA穩定[6]

circRNA由線狀RNA經反向剪接而生成

目前人類細胞中已有超過25,000種環狀RNA被發現[7],多位於細胞質[6],也有些源於基因內含子的環狀RNA(環狀內含子RNA,簡稱ciRNA)會留在細胞核中調控自身基因的表現[8]。有些環狀RNA可能可作為「miRNA海綿」(miRNA sponge)與miRNA結合,使後者無法和目標mRNA結合而阻斷RNA干擾[9][10]。環狀RNA還可能與一些RNA結合蛋白英语RNA-binding protein結合[5]、由內部核糖體進入位點(IRES)啟動轉譯而編碼蛋白質[11]、在細胞中運輸與儲存miRNA等[12]。環狀RNA的調控異常可能與多種癌症神經退化性疾病有關[13][14]

真核生物經反向剪接形成的環狀RNA外,生物還有數種其他生成環狀RNA的機制,例如第二型內含子英语group-II intron剪接的產物、某些藻類與古菌生成tRNA過程的中間產物等[7],另外D型肝炎類病毒的基因組也是環狀RNA[15]

參考文獻

编辑
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  3. ^ Pamudurti, Nagarjuna Reddy; Bartok, Osnat; Jens, Marvin; et al. Translation of CircRNAs. Molecular Cell. 2017, 66 (1): 9–21.e7. PMC 5387669 . PMID 28344080. doi:10.1016/j.molcel.2017.02.021.  
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  7. ^ 7.0 7.1 Nisar, Sabah; Bhat, Ajaz A.; Singh, Mayank; Karedath, Thasni; Rizwan, Arshi; Hashem, Sheema; Bagga, Puneet; Reddy, Ravinder; Jamal, Farrukh; Uddin, Shahab; Chand, Gyan. Insights Into the Role of CircRNAs: Biogenesis, Characterization, Functional, and Clinical Impact in Human Malignancies. Frontiers in Cell and Developmental Biology. 2021-02-05, 9. ISSN 2296-634X. PMC 7894079 . PMID 33614648. doi:10.3389/fcell.2021.617281. 
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  11. ^ Chen, CY; Sarnow, P. Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science. 1995, 268 (5209): 415–17. PMID 7536344. doi:10.1126/science.7536344. 
  12. ^ Hentze, MW; Preiss, T. Circular RNAs: splicing's enigma variations. The EMBO Journal. 2013, 32 (7): 923–25. PMC 3616293 . PMID 23463100. doi:10.1038/emboj.2013.53. 
  13. ^ Burd, CE; Jeck, WR; Liu, Y; Sanoff, HK; Wang, Z; Sharpless, NE. Expression of Linear and Novel Circular Forms of an INK4/ARF-Associated Non-coding RNA Correlates with Atherosclerosis Risk. PLOS Genetics. 2010, 6 (12): e1001223. PMC 2996334 . PMID 21151960. doi:10.1371/journal.pgen.1001233. 
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  15. ^ Harichandran K, Shen Y, Stephenson Tsoris S, Lee SC, Casey JL. Hepatitis Delta Antigen Regulates mRNA and Antigenome RNA Levels during Hepatitis Delta Virus Replication.. J Virol. 2019, 93 (8). PMC 6450126 . PMID 30728256. doi:10.1128/JVI.01989-18.