ページ「金木和也」と「RNA活性化」の間の差分
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'''RNA活性化'''（アールエヌエーかっせいか、{{Lang-en-short|RNA activation}}、'''RNAa'''）は、プロモーターを標的とした低分子二重鎖RNA（[[dsRNA]]）が[[転写 (生物学)|転写]]／[[エピジェネティック]]レベルで標的遺伝子の発現を誘導する、低分子RNA誘導および[[アルゴノート (タンパク質)|アルゴノート]]依存性の遺伝子制御現象である。RNAaは、2006年に発表されたLiらのPNAS論文で初めて報告され<ref name="li_pnas">{{cite journal | authors = Li LC, Okino ST, Zhao H, Pookot D, Place RF, Urakami S, Enokida H, Dahiya R | title = Small dsRNAs induce transcriptional activation in human cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 46 | pages = 17337–42 | date = November 2006 | pmid = 17085592 | pmc = 1859931 | doi = 10.1073/pnas.0607015103 }}{{psc|date=December 2011}}</ref>、このような遺伝子活性化現象を表すために、[[RNA干渉]]（[[RNAi]]）<ref name="li_pnas" />と対比させて「RNAa」という用語が作られた。RNAaを引き起こすdsRNAは、[[低分子活性化RNA]]（{{Lang-en-short|small activating RNA}}、[[saRNA]]）と呼ばれている<ref>Li, Longcheng; Dahiya, Rajvir. "[https://patents.google.com/patent/US20150104869A1/en?oq=20150104869 Small Activating RNA Molecules and Methods of Use]." U.S. Patent US 8,877,721 filed October 1, 2004, and issued November 4, 2014.</ref>。ヒトの細胞でRNAaが発見されて以来、他の多くのグループが、ヒト、非ヒト霊長類、ラットおよびマウスなどの異なる哺乳動物種や<ref name="ncb">{{cite journal | authors = Janowski BA, Younger ST, Hardy DB, Ram R, Huffman KE, Corey DR | title = Activating gene expression in mammalian cells with promoter-targeted duplex RNAs | journal = Nature Chemical Biology | volume = 3 | issue = 3 | pages = 166–73 | date = March 2007 | pmid = 17259978 | doi = 10.1038/nchembio860 }}</ref><ref name="circres">{{cite journal | authors = Turunen MP, Lehtola T, Heinonen SE, Assefa GS, Korpisalo P, Girnary R, Glass CK, Väisänen S, Ylä-Herttuala S | title = Efficient regulation of VEGF expression by promoter-targeted lentiviral shRNAs based on epigenetic mechanism: a novel example of epigenetherapy | journal = Circulation Research | volume = 105 | issue = 6 | pages = 604–9 | date = September 2009 | pmid = 19696410 | doi = 10.1161/CIRCRESAHA.109.200774 | doi-access = free }}</ref><ref>{{cite journal | authors = Huang V, Qin Y, Wang J, Wang X, Place RF, Lin G, Lue TF, Li LC | title = RNAa is conserved in mammalian cells | journal = PLOS One | volume = 5 | issue = 1 | pages = e8848 | date = January 2010 | pmid = 20107511 | pmc = 2809750 | doi = 10.1371/journal.pone.0008848 | editor1-last = Jin | editor1-first = Dong-Yan }}</ref><ref name="coreychembio">{{cite journal | authors = Matsui M, Sakurai F, Elbashir S, Foster DJ, Manoharan M, Corey DR | title = Activation of LDL receptor expression by small RNAs complementary to a noncoding transcript that overlaps the LDLR promoter | journal = Chemistry & Biology | volume = 17 | issue = 12 | pages = 1344–55 | date = December 2010 | pmid = 21168770 | pmc = 3071588 | doi = 10.1016/j.chembiol.2010.10.009 }}</ref>、植物<ref>{{cite journal | authors = Shibuya K, Fukushima S, Takatsuji H | title = RNA-directed DNA methylation induces transcriptional activation in plants | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 5 | pages = 1660–5 | date = February 2009 | pmid = 19164525 | pmc = 2629447 | doi = 10.1073/pnas.0809294106 }}</ref>、線虫<ref name=":1">{{cite journal | authors = Seth M, Shirayama M, Gu W, Ishidate T, Conte D, Mello CC | title = The C. elegans CSR-1 argonaute pathway counteracts epigenetic silencing to promote germline gene expression | journal = Developmental Cell | volume = 27 | issue = 6 | pages = 656–63 | date = December 2013 | pmid = 24360782 | pmc = 3954781 | doi = 10.1016/j.devcel.2013.11.014 }}</ref><ref name="turner_cellcycle">{{cite journal | authors = Turner MJ, Jiao AL, Slack FJ | title = Autoregulation of lin-4 microRNA transcription by RNA activation (RNAa) in C. elegans | journal = Cell Cycle | volume = 13 | issue = 5 | pages = 772–81 | date = Jan 7, 2014 | pmid = 24398561 | pmc = 3979913 | doi = 10.4161/cc.27679 }}</ref>で同様の観察を行い、RNAaが進化的に保存された遺伝子制御機構であることが示唆されている。
RNAaは一般的に、外因性と内因性の2つのカテゴリーに分類される。外因性RNAaは、遺伝子のプロモーター<ref name="li_pnas" />や3'末端<ref>{{cite journal | authors = Yue X, Schwartz JC, Chu Y, Younger ST, Gagnon KT, Elbashir S, Janowski BA, Corey DR | title = Transcriptional regulation by small RNAs at sequences downstream from 3' gene termini | journal = Nature Chemical Biology | volume = 6 | issue = 8 | pages = 621–9 | date = August 2010 | pmid = 20581822 | pmc = 3909968 | doi = 10.1038/nchembio.400 }}</ref>などの非コード配列を標的として人工的に設計されたsaRNAによって引き起こされるもので、これらのsaRNAは化学的に合成されたり<ref name="li_pnas" />、短ヘアピンRNA（[[shRNA]]）として発現させたりすることができる<ref name="circres" />。一方、内在性RNAaでは、遺伝子発現のアップレギュレーションは、哺乳類細胞<ref name=":2" /><ref name=":3" />や線虫のmiRNA、線虫の22G RNA<ref name="turner_cellcycle" />など、自然に存在する内在性低分子RNAによって導かれる<ref name=":1" />。
== 機構 ==
RNAaの分子メカニズムは完全には解明されていない。RNAiと同様に、哺乳類のRNAaは、[[アルゴノート (タンパク質)|アルゴノートタンパク質]]のAgoクレードのメンバー（特にAgo2）を必要とするが<ref name="li_pnas" /><ref name="coreynar">{{cite journal | authors = Chu Y, Yue X, Younger ST, Janowski BA, Corey DR | title = Involvement of argonaute proteins in gene silencing and activation by RNAs complementary to a non-coding transcript at the progesterone receptor promoter | journal = Nucleic Acids Research | volume = 38 | issue = 21 | pages = 7736–48 | date = November 2010 | pmid = 20675357 | pmc = 2995069 | doi = 10.1093/nar/gkq648 }}</ref>、RNAiとは異なる動態を持つことが明らかになっている<ref name="LiLC">{{cite book |chapter-url=https://books.google.com/books?id=r67Lrf9r9XEC&pg=PA189 |last=Li |first=Long-Cheng |year=2008 |chapter=Small RNA-mediated gene activation |editor1-first=Kevin V |editor1-last=Morris |title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity |publisher=Caister Academic Press |isbn=978-1-904455-25-7 |pages=189–99}}</ref>。RNAiとは対照的に、プロモーターを標的としたsaRNAは、エピジェネティックな変化に伴う遺伝子発現の長期的な活性化を誘導する<ref name="WIREsRNA">{{cite journal | authors = Portnoy V, Huang V, Place RF, Li LC | title = Small RNA and transcriptional upregulation | journal = Wiley Interdisciplinary Reviews: RNA | volume = 2 | issue = 5 | pages = 748–60 | year = 2011 | pmid = 21823233 | pmc = 3154074 | doi = 10.1002/wrna.90 }}</ref>。現在のところ、saRNAは最初にAgoタンパク質によってロードされ、処理されてAgo-RNA複合体を形成し、次にRNAによってプロモーター標的に誘導されると考えられている。その標的は、プロモーター<ref name="coreychembio" /><ref name="coreynar" />または染色体DNAと重複する非コード転写物の可能性がある<ref name="WIREsRNA" /><ref>{{cite journal | authors = Meng X, Jiang Q, Chang N, Wang X, Liu C, Xiong J, Cao H, Liang Z | title = Small activating RNA binds to the genomic target site in a seed-region-dependent manner | journal = Nucleic Acids Research | volume = 44 | issue = 5 | pages = 2274–82 | date = March 2016 | pmid = 26873922 | pmc = 4797303 | doi = 10.1093/nar/gkw076 }}</ref>。RNAをロードしたAgoは、次に、核DNAヘリカーゼIIとしても知られる{{仮リンク|RNAヘリカーゼA|en|RNA Helicase A|label=RHA}}や、{{仮リンク|CTR9|en|CTR9}}などの他のタンパク質を動員して、RNA誘導転写活性化（RITA）複合体を形成する。RITAは[[RNAポリメラーゼII|RNAP II]]と直接相互作用することで[[転写 (生物学)#Pol II系遺伝子（構造遺伝子など大部分の遺伝子）における転写の開始|転写開始]]を促進し、H2Bの[[ユビキチン]]化を刺激することで有効な転写伸長を促進する<ref>{{cite journal | authors = Portnoy V, Lin SH, Li KH, Burlingame A, Hu ZH, Li H, Li LC | title = saRNA-guided Ago2 targets the RITA complex to promoters to stimulate transcription | journal = Cell Research | volume = 26 | issue = 3 | pages = 320–35 | date = March 2016 | pmid = 26902284 | pmc = 4783471 | doi = 10.1038/cr.2016.22 }}</ref><ref>{{cite journal | authors = Voutila J, Reebye V, Roberts TC, Protopapa P, Andrikakou P, Blakey DC, Habib R, Huber H, Saetrom P, Rossi JJ, Habib NA | title = Development and Mechanism of Small Activating RNA Targeting CEBPA, a Novel Therapeutic in Clinical Trials for Liver Cancer | journal = Molecular Therapy | volume = 25 | issue = 12 | pages = 2705–2714 | date = December 2017 | pmid = 28882451 | pmc = 5768526 | doi = 10.1016/j.ymthe.2017.07.018 }}</ref>。
== 内因性RNAa ==
2008年、Placeらは、いくつかのヒト遺伝子のプロモーター上に[[miRNA]] miR-373の標的を同定し、miR-373の模倣体をヒト細胞に導入すると、予測される標的遺伝子の発現が誘導されることを発見した。この研究は、RNAaが天然に存在する[[非コードRNA]]（[[ncRNA]]）によって媒介される可能性があることを示す最初の例となった<ref name=":2">{{cite journal | authors = Place RF, Li LC, Pookot D, Noonan EJ, Dahiya R | title = MicroRNA-373 induces expression of genes with complementary promoter sequences | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 5 | pages = 1608–13 | date = February 2008 | pmid = 18227514 | pmc = 2234192 | doi = 10.1073/pnas.0707594105 }}{{psc|date=December 2011}}</ref>。2011年、Huangらはさらに、マウス細胞を用いて、miRNAを介した内因性RNAaが生理学的状況で機能し、がん細胞が成長の優位性を得るために利用している可能性があることを実証した<ref name=":3">{{cite journal | authors = Huang V, Place RF, Portnoy V, Wang J, Qi Z, Jia Z, Yu A, Shuman M, Yu J, Li LC | title = Upregulation of Cyclin B1 by miRNA and its implications in cancer | journal = Nucleic Acids Research | volume = 40 | issue = 4 | pages = 1695–707 | date = February 2012 | pmid = 22053081 | pmc = 3287204 | doi = 10.1093/nar/gkr934 }}{{psc|date=December 2011}}</ref>。それ以来、多くのmiRNAが、遺伝子プロモーター<ref>{{cite journal | authors = Matsui M, Chu Y, Zhang H, Gagnon KT, Shaikh S, Kuchimanchi S, Manoharan M, Corey DR, Janowski BA | title = Promoter RNA links transcriptional regulation of inflammatory pathway genes | journal = Nucleic Acids Research | volume = 41 | issue = 22 | pages = 10086–109 | date = December 2013 | pmid = 23999091 | pmc = 3905862 | doi = 10.1093/nar/gkt777 }}</ref><ref>{{cite journal | authors = Dharap A, Pokrzywa C, Murali S, Pandi G, Vemuganti R | title = MicroRNA miR-324-3p induces promoter-mediated expression of RelA gene | journal = PLOS One | volume = 8 | issue = 11 | pages = e79467 | date = 2013 | pmid = 24265774 | pmc = 3827167 | doi = 10.1371/journal.pone.0079467 }}</ref><ref name=":0">{{cite journal | authors = Chaluvally-Raghavan P, Jeong KJ, Pradeep S, Silva AM, Yu S, Liu W, Moss T, Rodriguez-Aguayo C, Zhang D, Ram P, Liu J, Lu Y, Lopez-Berestein G, Calin GA, Sood AK, Mills GB | title = Direct Upregulation of STAT3 by MicroRNA-551b-3p Deregulates Growth and Metastasis of Ovarian Cancer | journal = Cell Reports | volume = 15 | issue = 7 | pages = 1493–1504 | date = May 2016 | pmid = 27160903 | pmc = 4914391 | doi = 10.1016/j.celrep.2016.04.034 }}</ref><ref>{{cite journal | authors = Li S, Wang C, Yu X, Wu H, Hu J, Wang S, Ye Z | title = miR-3619-5p inhibits prostate cancer cell growth by activating CDKN1A expression | journal = Oncology Reports | volume = 37 | issue = 1 | pages = 241–248 | date = January 2017 | pmid = 27878260 | doi = 10.3892/or.2016.5250 | doi-access = free }}</ref>またはエンハンサー<ref>{{cite journal | authors = Xiao M, Li J, Li W, Wang Y, Wu F, Xi Y, Zhang L, Ding C, Luo H, Li Y, Peng L, Zhao L, Peng S, Xiao Y, Dong S, Cao J, Yu W | title = MicroRNAs activate gene transcription epigenetically as an enhancer trigger | journal = RNA Biology | volume = 14 | issue = 10 | pages = 1326–1334 | date = October 2017 | pmid = 26853707 | pmc = 5711461 | doi = 10.1080/15476286.2015.1112487 }}</ref>を標的とすることで遺伝子の発現をアップレギュレートし、それによって重要な生物学的役割を果たしていることが明らかになった。その好例が、卵巣がんで増幅により過剰発現しているmiR-551b-3pである<ref name=":0" />。miR-551b-3pは、{{仮リンク|STAT3|en|STAT3}}のプロモーターを標的としてその転写を増加させることにより、卵巣がん細胞に[[アポトーシス]]に対する抵抗性と増殖の優位性をもたらす<ref name=":0" />。
線虫の皮下胚葉細胞では、{{仮リンク|lin-4マイクロRNA前駆体|en|lin-4 microRNA precursor|label=lin-4}} miRNAの転写は、そのプロモーターにある保存されたlin-4相補的要素に結合するlin-4自身によって正に制御されており、正の自己調節ループを構成している<ref name="turner_cellcycle" /><ref>{{cite journal | authors = Vaschetto LM | title = miRNA activation is an endogenous gene expression pathway | journal = RNA Biology | pages = 1–3 | date = April 2018 | pmid = 29537927 | doi = 10.1080/15476286.2018.1451722 | pmc = 6152443 }}</ref>。
線虫では、アルゴノートCSR-1は、[[RNA依存性RNAポリメラーゼ]]に由来する22G低分子RNAと相互作用し、生殖細胞系発現の転写物に対するアンチセンスを用いて、エピジェネティックな活性化を促進することにより、{{仮リンク|Piwi|en|Piwi}}-{{仮リンク|Piwi結合RNA|en|Piwi-interacting RNA|label=piRNA}}を介した[[サイレンシング]]からこれらのmRNAを保護している<ref>{{cite journal | authors = Conine CC, Moresco JJ, Gu W, Shirayama M, Conte D, Yates JR, Mello CC | title = Argonautes promote male fertility and provide a paternal memory of germline gene expression in C. elegans | journal = Cell | volume = 155 | issue = 7 | pages = 1532–44 | date = December 2013 | pmid = 24360276 | pmc = 3924572 | doi = 10.1016/j.cell.2013.11.032 }}</ref><ref>{{cite journal | authors = Wedeles CJ, Wu MZ, Claycomb JM | title = Protection of germline gene expression by the C. elegans Argonaute CSR-1 | journal = Developmental Cell | volume = 27 | issue = 6 | pages = 664–71 | date = December 2013 | pmid = 24360783 | doi = 10.1016/j.devcel.2013.11.016 | doi-access = free }}</ref>。
哺乳類細胞において、内在性RNAaによる遺伝子制御がどの程度広く行われているかは、現在のところ不明である。これまでの研究で、miRNA<ref>{{cite journal | authors = Paugh SW, Coss DR, Bao J, Laudermilk LT, Grace CR, Ferreira AM, Waddell MB, Ridout G, Naeve D, Leuze M, LoCascio PF, Panetta JC, Wilkinson MR, Pui CH, Naeve CW, Uberbacher EC, Bonten EJ, Evans WE | title = MicroRNAs Form Triplexes with Double Stranded DNA at Sequence-Specific Binding Sites; a Eukaryotic Mechanism via which microRNAs Could Directly Alter Gene Expression | journal = PLoS Computational Biology | volume = 12 | issue = 2 | pages = e1004744 | date = February 2016 | pmid = 26844769 | pmc = 4742280 | doi = 10.1371/journal.pcbi.1004744 }}</ref>とAgoタンパク質（Ago1）<ref>{{cite journal | authors = Huang V, Zheng J, Qi Z, Wang J, Place RF, Yu J, Li H, Li LC | title = Ago1 Interacts with RNA polymerase II and binds to the promoters of actively transcribed genes in human cancer cells | journal = PLoS Genetics | volume = 9 | issue = 9 | pages = e1003821 | date = 2013 | pmid = 24086155 | pmc = 3784563 | doi = 10.1371/journal.pgen.1003821 }}</ref>の両方が、ヒトゲノムの多数の部位、特にプロモーター領域に結合し、遺伝子の転写に大きなプラス効果をもたらすことが明らかになっている。
== 応用 ==
RNAaは、ベクターを用いた遺伝子の大量発現の代わりに、遺伝子機能を研究するために用いられてきた<ref name="wangcanres">{{cite journal | authors = Wang J, Place RF, Huang V, Wang X, Noonan EJ, Magyar CE, Huang J, Li LC | title = Prognostic value and function of KLF4 in prostate cancer: RNAa and vector-mediated overexpression identify KLF4 as an inhibitor of tumor cell growth and migration | journal = Cancer Research | volume = 70 | issue = 24 | pages = 10182–91 | date = December 2010 | pmid = 21159640 | pmc = 3076047 | doi = 10.1158/0008-5472.CAN-10-2414 }}</ref>。これまでの研究により、生体内（in vivo）でのRNAaの存在が証明されており、がんや非がん性疾患の治療に応用できる可能性がある<ref name="circres" /><ref>{{cite journal | authors = Chen R, Wang T, Rao K, Yang J, Zhang S, Wang S, Liu J, Ye Z | title = Up-regulation of VEGF by small activator RNA in human corpus cavernosum smooth muscle cells | journal = The Journal of Sexual Medicine | volume = 8 | issue = 10 | pages = 2773–80 | date = October 2011 | pmid = 21819543 | doi = 10.1111/j.1743-6109.2011.02412.x }}</ref><ref name="KangCancerRes">{{cite journal | authors = Kang MR, Yang G, Place RF, Charisse K, Epstein-Barash H, Manoharan M, Li LC | title = Intravesical delivery of small activating RNA formulated into lipid nanoparticles inhibits orthotopic bladder tumor growth | journal = Cancer Research | volume = 72 | issue = 19 | pages = 5069–79 | date = October 2012 | pmid = 22869584 | doi = 10.1158/0008-5472.can-12-1871 | doi-access = free }}</ref><ref name="PlaceMTNA">{{cite journal | authors = Place RF, Wang J, Noonan EJ, Meyers R, Manoharan M, Charisse K, Duncan R, Huang V, Wang X, Li LC | title = Formulation of Small Activating RNA Into Lipidoid Nanoparticles Inhibits Xenograft Prostate Tumor Growth by Inducing p21 Expression | journal = Molecular Therapy. Nucleic Acids | volume = 1 | issue = 3 | pages = e15 | date = March 2012 | pmid = 23343884 | pmc = 3381590 | doi = 10.1038/mtna.2012.5 }}</ref><ref>{{cite journal | authors = Yoon S, Huang KW, Reebye V, Mintz P, Tien YW, Lai HS, Sætrom P, Reccia I, Swiderski P, Armstrong B, Jozwiak A, Spalding D, Jiao L, Habib N, Rossi JJ | title = Targeted Delivery of C/EBPα -saRNA by Pancreatic Ductal Adenocarcinoma-specific RNA Aptamers Inhibits Tumor Growth In Vivo | journal = Molecular Therapy | volume = 24 | issue = 6 | pages = 1106–1116 | date = June 2016 | pmid = 26983359 | pmc = 4923325 | doi = 10.1038/mt.2016.60 }}</ref><ref>{{cite journal | authors = Huan H, Wen X, Chen X, Wu L, Liu W, Habib NA, Bie P, Xia F | title = C/EBPα Short-Activating RNA Suppresses Metastasis of Hepatocellular Carcinoma through Inhibiting EGFR/β-Catenin Signaling Mediated EMT | journal = PLOS One | volume = 11 | issue = 4 | pages = e0153117 | date = 2016-01-01 | pmid = 27050434 | pmc = 4822802 | doi = 10.1371/journal.pone.0153117 }}</ref><ref>{{cite journal | authors = Li C, Jiang W, Hu Q, Li LC, Dong L, Chen R, Zhang Y, Tang Y, Thrasher JB, Liu CB, Li B | title = Enhancing DPYSL3 gene expression via a promoter-targeted small activating RNA approach suppresses cancer cell motility and metastasis | journal = Oncotarget | volume = 7 | issue = 16 | pages = 22893–910 | date = April 2016 | pmid = 27014974 | pmc = 5008410 | doi = 10.18632/oncotarget.8290 }}</ref><ref>{{cite journal | authors = Reebye V, Huang KW, Lin V, Jarvis S, Cutilas P, Dorman S, Ciriello S, Andrikakou P, Voutila J, Saetrom P, Mintz PJ, Reccia I, Rossi JJ, Huber H, Habib R, Kostomitsopoulos N, Blakey DC, Habib NA | title = Gene activation of CEBPA using saRNA: preclinical studies of the first in human saRNA drug candidate for liver cancer | journal = Oncogene | volume = 37 | issue = 24 | pages = 3216–3228 | date = June 2018 | pmid = 29511346 | pmc = 6013054 | doi = 10.1038/s41388-018-0126-2 }}</ref>。
2016年6月、英国のMiNA Therapeutics社は、{{仮リンク|CEBPA|en|CEBPA}}遺伝子の活性化を試み、肝臓がん患者を対象とした初のsaRNA医薬品MTL-CEBPAの第I相試験の開始を発表した<ref>{{Cite web|url = http://www.businesswire.com/news/home/20160602005089/en/|title = MiNA Therapeutics Announces Initiation of Phase I Clinical Study of MTL-CEBPA in Patients with Liver Cancer {{!}} Business Wire|website = www.businesswire.com|access-date = 2016-06-06}}</ref><ref>{{Cite web|url = https://clinicaltrials.gov/ct2/show/NCT02716012|title = First-in-Human Safety and Tolerability Study of MTL-CEBPA in Patients With Advanced Liver Cancer - Full Text View - ClinicalTrials.gov|website = clinicaltrials.gov|access-date = 2016-06-06}}</ref>。
== 参照項目 ==
{{Reflist|colwidth=30em}}
{{refbegin}}
* {{cite journal | authors = Check E | title = RNA interference: hitting the on switch | journal = Nature | volume = 448 | issue = 7156 | pages = 855–8 | date = August 2007 | pmid = 17713502 | doi = 10.1038/448855a | doi-access = free }}
* {{cite book |author=Morris, Kevin L. |title=RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity |publisher=Caister Academic Press |___location=Norfolk, England |year=2008 |isbn=1-904455-25-5 |url=http://www.horizonpress.com/rnareg}}
* {{cite book |author=Jorg Tost |title=Epigenetics |publisher=Caister Academic Press |___location=Norfolk, England |year=2008 |isbn=1-904455-23-9 |url=http://www.horizonpress.com/epi}}
* {{cite book |author=Long-Cheng Li |title=RNA Activation |publisher=Springer Nature |___location=Singapore |year=2017 |isbn=978-981-10-4310-9 |url=https://www.springer.com/us/book/9789811043093}}
* {{cite journal | authors = Garber K | title = Genetics. Small RNAs reveal an activating side | journal = Science | volume = 314 | issue = 5800 | pages = 741–2 | date = November 2006 | pmid = 17082428 | doi = 10.1126/science.314.5800.741a }}
{{refend}}
== 外部リンク ==
*RNAa FAQs [http://www.urogene.org/RNAa-FAQs.html Li Lab, University of California San Francisco]
*How to get your genes switched on. [https://www.newscientist.com/channel/life/genetics/mg19225780.149-how-to-get-your-genes-switched-on.html New Scientist 16 November 2006]
[[Category:リボ核酸]]
[[Category:遺伝子発現]]
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