環狀RNA

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

  1. ^ 1.0 1.1 Salzman, J; Gawad, C.; Wang, P.L.; Lacayo, N; Brown, PO. Circular RNAs are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types. PLOS ONE. 2012, 7 (2): e30733. Bibcode:2012PLoSO...730733S. PMC 3270023. PMID 22319583. doi:10.1371/journal.pone.0030733. 
  2. ^ New study shows circular RNA can encode for proteins. Science Daily. 2017 [3 May 2018]. 
  3. ^ Pamudurti, Nagarjuna Reddy; Bartok, Osnat; Jens, Marvin; 等. Translation of CircRNAs. Molecular Cell. 2017, 66 (1): 9–21.e7. PMC 5387669. PMID 28344080. doi:10.1016/j.molcel.2017.02.021.  
  4. ^ Guo, J.U.; Agarwal, V; Guo, H; Bartel, DP. Expanded identification and characterization of mammalian circular RNAs. Genome Biology. 2014, 15 (7): 409. PMC 4165365. PMID 25070500. doi:10.1186/s13059-014-0409-z. 
  5. ^ 5.0 5.1 Wilusz, J.E.; Sharp, PA. A Circuitous Route to Noncoding RNA (PDF). Science. 2013, 340 (6131): 440–41. Bibcode:2013Sci...340..440W. PMC 4063205. PMID 23620042. doi:10.1126/science.1238522. 
  6. ^ 6.0 6.1 6.2 Jeck, WR; Sorrentino, JA; Wang, K; 等. Circular RNAs are abundant, conserved, and associated with ALU repeats.. RNA. 2013, 19 (2): 141–57. PMC 3543092. PMID 23249747. doi:10.1261/rna.035667.112. 
  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. 
  8. ^ Zhang, Y; Zhang, XO; Chen, T; Xiang, JF; Yin, QF; Xing, YH; Zhu, S; Yang, L; Chen, LL. Circular Intronic Long Non-coding RNAs. Molecular Cell. 2013, 51 (6): 1–15. PMID 24035497. doi:10.1016/j.molcel.2013.08.017. 
  9. ^ Ebert, MS; Sharp, PA. MicroRNA sponges: progress and possibilities. RNA. 2010, 16 (11): 2043–50. PMC 2957044. PMID 20855538. doi:10.1261/rna.2414110. 
  10. ^ Hansen, T.B.; Jensen, TI; Clausen, BH; Bramsen, JB; Finsen, B; Damgaard, CK; Kjems, J. Natural RNA circles function as efficient microRNA sponges. Nature. 2013, 495 (7441): 384–88. Bibcode:2013Natur.495..384H. PMID 23446346. doi:10.1038/nature11993. 
  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. 
  14. ^ Dube, U; Del-Aguila, JL; Li, Z; Budde, JP; Jiang, S; Hsu, S; Ibanez, L; Fernandez, MV; 等. An atlas of cortical circular RNA expression in Alzheimer disease brains demonstrates clinical and pathological associations.. Nature Neuroscience. 2019, 22 (11): 1903–1912. PMC 6858549. PMID 31591557. doi:10.1038/s41593-019-0501-5. 
  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.