长链非编码RNA在生物体中的调控作用
收稿日期: 2013-09-29
修回日期: 2013-11-21
网络出版日期: 2014-02-25
基金资助
国家重点基础研究发展计划(973计划)项目(编号:2011CB504203), 国家自然科学基金项目(编号:31000579; 31371325), 四川省创新团队发展计划项目(编号:2011JTD0026)和教育部新世纪优秀人才支持计划(编号:NCET-10-0599)资助
In vivo functions of long non-coding RNAs
Received date: 2013-09-29
Revised date: 2013-11-21
Online published: 2014-02-25
长链非编码RNA(Long non-coding RNA, lncRNA)的发现是基因组学和分子生物学研究领域的重要进展。lncRNA在生命活动中具有重要的调节功能, 其表达紊乱与多种人类疾病的发生发展密切相关。研究表明, 几乎所有的调控性lncRNA通过与不同种类的生物大分子, 如DNA、RNA和蛋白质发生相互作用而行使其功能。文章概述了lncRNA在表观遗传学水平、转录水平及转录后水平调控基因表达的效应机制, 并探讨了lncRNA如何在肿瘤发生和宿主防御过程中行使功能。不同于小分子ncRNA通过碱基互补配对调控靶基因的表达, 大多数已鉴定的lncRNA通过调节蛋白质活性或维持蛋白质复合物的完整性发挥其生物学功能。因此, 鉴定lncRNA-蛋白质相互作用可能是理解lncRNA功能的首要任务。
关键词: 长链非编码RNA; 基因表达; RNA-蛋白质相互作用
李灵, 宋旭 . 长链非编码RNA在生物体中的调控作用[J]. 遗传, 2014 , 36(3) : 228 -236 . DOI: 10.3724/SP.J.1005.2014.0228
Advances in genomics and molecular biology have led to discovery of a large group of previous uncharacterized long non-noncoding RNAs (lncRNAs). Whether all of these transcripts are functional remains to be elucidated, but emerging evidence indicates that many lncRNAs play roles in multiple biological processes and that dysregulation of lncRNAs is often associated with diseases. Of significant interest, recent studies suggest that almost all of the regulatory lncRNAs function through interacting with different biological macromolecules such as DNA, RNA, and protein. In this review, we summarize the mechanisms by which lncRNAs regulate gene expression at epigenetic, transcriptional and post-transcriptional levels, and discuss the role of lncRNAs in tumorigenesis and host defense. Distinct from small ncRNAs that regulate gene expression mainly through base pairing to target transcripts, most identified lncRNAs function by regu-lating protein activity or maintaining the integrity of protein complexes. As a result, identification and characterization of the lncRNA-protein interactions may be the primary task to decode functional lncRNAs.
Key words: long non-coding RNAs; gene expression; RNA-protein interaction
[1] ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature, 2007, 447(7146): 799– 816. <\p>
[2] Carthew RW, Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs. Cell, 2009, 136(4): 642–655. <\p>
[3] Liu HJ, Wang XR, Wang HD, Wu JJ, Ren J, Meng LF, Wu QF, Dong HS, Wu J, Kao TY, Ge Q, Wu ZX, Yuh CH, Shan G. Escherichia coli noncoding RNAs can affect gene expression and physiology of Caenorhabditis elegans. Nat Commun, 2012, 3: 1073. <\p>
[4] Yu FY, Yao HR, Zhu P, Zhang XC, Pan QH, Gong C, Huang YJ, Hu XQ, Su FX, Lieberman J, Song E. let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell, 2007, 131(6): 1109–1123. <\p>
[5] Zhang L, Hou DX, Chen X, Li DH, Zhu LY, Zhang YJ, Li J, Bian Z, Liang XY, Cai X, Yin Y, Wang C, Zhang TF, Zhu DH, Zhang DM, Xu J, Chen Q, Ba Y, Liu J, Wang Q, Chen JQ, Wang J, Wang M, Zhang QP, Zhang JF, Zen K, Zhang CY. Exogenous plant MIR168a specifically targets mammalian LDLRAP1: evidence of cross-kingdom regu-lation by microRNA. Cell Res, 2012, 22(1): 107–126. <\p>
[6] Zhao S, Gou LT, Zhang M, Zu LD, Hua MM, Hua Y, Shi HJ, Li Y, Li JS, Li DS, Wang ED, Liu MF. piRNA-triggered MIWI ubiquitination and removal by APC/C in late spermatogenesis. Dev Cell, 2013, 24(1): 13–25. <\p>
[7] Wang Y, Chen J, Wei G, He H, Zhu X, Xiao T, Yuan J, Dong B, He S, Skogerb G, Chen R. The Caenorhabditis elegans intermediate-size transcriptome shows high de-gree of stage-specific expression. Nucleic Acids Res, 2011, 39(12): 5203–5214. <\p>
[8] Guttman M, Amit I, Garber M, French C, Lin MF, Feldser D, Huarte M, Zuk O, Carey BW, Cassady JP, Cabili MN, Jaenisch R, Mikkelsen TS, Jacks T, Hacohen N, Bernstein BE, Kellis M, Regev A, Rinn JL, Lander ES. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature, 2009, 458(7235): 223–227. <\p>
[9] Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell, 2011, 147(7): 1537–1550. <\p>
[10] Spizzo R, Almeida MI, Colombatti A, Calin GA. Long non-coding RNAs and cancer: a new frontier of transla-tional research? Oncogene, 2012, 31(43): 4577–4587. <\p>
[11] Tsai MC, Spitale RC, Chang HY. Long intergenic non-coding RNAs: new links in cancer progression. Cancer Res, 2011, 71(1): 3–7. <\p>
[12] McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, Hinds DA, Pennacchio LA, Tybjaerg- Hansen A, Folsom AR, Boerwinkle E, Hobbs HH, Cohen JC. A common allele on chromosome 9 associated with coronary heart disease. Science, 2007, 316(5830): 1488– 1491. <\p>
[13] Johnson R. Long non-coding RNAs in Huntington’s dis-ease neurodegeneration. Neurobiol Dis, 2012, 46(2): 245– 254. <\p>
[14] Tan L, Yu JT, Hu N, Tan L. Non-coding RNAs in Alz-heimer’s disease. Mol Neurobiol, 2013, 47(1): 382–393. <\p>
[15] Ponting CP, Oliver PL, Reik W. Evolution and functions of long noncoding RNAs. Cell, 2009, 136 (4): 629–641. <\p>
[16] Du Toit A. Non-coding RNA: RNA stability control by Pol II. Nat Rev Mol Cell Biol, 2013, 14(3): 128. <\p>
[17] Cheng J, Kapranov P, Drenkow J, Dike S, Brubaker S, Patel S, Long J, Stern D, Tammana H, Helt G, Sementchenko V, Piccolboni A, Bekiranov S, Bailey DK, Ganesh M, Ghosh S, Bell I, Gerhard DS, Gingeras TR. Transcrip-tional maps of 10 human chromosomes at 5-nucleotide resolution. Science, 2005, 308(5725): 1149–1154. <\p>
[18] Goodrich JA, Kugel JF. Dampening DNA binding: a common mechanism of transcriptional repression for both ncRNAs and protein domains. RNA Biol, 2010, 7(3): 305&ndash
/
| 〈 |
|
〉 |