Recognition of self and non-self in the genome by small RNAs and chromatin factors

• Project/Area Number: 15H05583
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: System genome science
• Research Institution: Keio University
• Principal Investigator: Iwasaki Yuka 慶應義塾大学, 医学部(信濃町), 講師 (80612647)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥23,400,000 (Direct Cost: ¥18,000,000、Indirect Cost: ¥5,400,000); Fiscal Year 2017: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000); Fiscal Year 2016: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2015: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: 小分子RNA / piRNA / トランスポゾン / 転写制御 / エピゲノム制御 / 非コードRNA / RNAサイレンシング / RNA結合タンパク質 / クロマチン因子 / small RNA / RNA-タンパク質複合体 / ゲノム安定性 / Piwi-piRNA複合体 / 標的認識 / リンカーヒストン

Outline of Final Research Achievements

PIWI-interacting RNAs (piRNAs) are germline-specific small RNAs, which form the effector complexes with PIWI proteins to preserve the genome integrity by repressing transposable elements (TEs). Among PIWI-clade proteins in Drosophila, Piwi is known to transcriptionally silence their targets via heterochromatin formation. In this study, following points were analyzed in order to reveal the molecular mechanism of RNA silencing by Piwi-piRNAs: how piRNAs are assigned to three different types of PIWI proteins, how heterochromatin is induced by Piwi-piRNAs, and how Piwi-piRNA complex is guided to their target locus. The results obtained from these analyses revealed the mechanism how small RNAs and chromatin factors can recognize self and non-self in the genome.

Research Products

• [Journal Article] Hierarchical roles of mitochondrial Papi and Zucchini in Bombyx germline piRNA biogenesis. (2018)
  • Author(s): Nishida Kazumichi M.、Sakakibara Kazuhiro、Iwasaki Yuka W.、Yamada Hiromi、Murakami Ryo、Murota Yukiko、Kawamura Takeshi、Kodama Tatsuhiko、Siomi Haruhiko、Siomi Mikiko C.
  • Journal Title: Nature Volume: 555 Pages: 260-264
  • DOI: 10.1038/nature25788
  • Peer Reviewed / Open Access
• [Journal Article] Profiling Open Chromatin Structure in the Ovarian Somatic Cells Using ATAC-seq (2018)
  • Author(s): Murano K, Iwasaki YW, Siomi H.
  • Journal Title: Methods in Molecluar Biology (Argonaute Proteins) Volume: 1680 Pages: 165-177
  • DOI: 10.1007/978-1-4939-7339-2_11
  • Peer Reviewed
• [Journal Article] Deep sequencing and high-throughput analysis of PIWI-associated small RNAs. (2017)
  • Author(s): Iwasaki Yuka W.、Ishino Kyoko、Siomi Haruhiko
  • Journal Title: Methods Volume: 126 Pages: 66-75
  • DOI: 10.1016/j.ymeth.2017.05.020
  • Peer Reviewed
• [Journal Article] 内在性小分子RNAの網羅的解析手法 (2017)
  • Author(s): 岩崎由香
  • Journal Title: 実験医学（エピジェネティクス実験スタンダード） Volume: - Pages: 311-322
• [Journal Article] Profiling open chromatin structure in the Ovarian Somatic Cells using ATAC-seq (2017)
  • Author(s): Murano K, Iwasaki YW, Siomi H
  • Journal Title: Methods in Molecular Biology Volume: 印刷中
  • Acknowledgement Compliant
• [Journal Article] 内在性小分子RNAの網羅的解析手法 (2017)
  • Author(s): 岩崎由香
  • Journal Title: 実験医学 Volume: 印刷中
• [Journal Article] Piwi modulates chromatin accessibility by regulating multiple factors including Histone H1 to repress transposons (2016)
  • Author(s): Iwasaki YW, Murano K, Ishizu H, Shibuya A, Iyoda Y, Siomi MC, Siomi H, Saito K
  • Journal Title: Molecular Cell Volume: 63 Pages: 408-419
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Loss of l(3)mbt leads to acquisition of the ping-pong cycle in Drosophila ovarian somatic cells. (2016)
  • Author(s): Sumiyoshi T, Sato K, Yamamoto H, Iwasaki YW, Siomi H, Siomi MC
  • Journal Title: Genes Dev. Volume: 30 Pages: 1617-1622
  • DOI: 10.1101/gad.283929.116
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PiwiはヒストンH1を介したクロマチンの構造の制御により標的となるトランスポゾンを抑制する (2016)
  • Author(s): 岩崎由香，塩見春彦，齋藤都暁
  • Journal Title: First author’s ライフサイエンス新着論文レビュー Volume: -
  • Open Access
• [Journal Article] Krimper Enforces an Antisense Bias on piRNA Pools by Binding AGO3 in the Drosophila Germline. (2015)
  • Author(s): Sato K, Iwasaki YW (equal contribution), Shibuya A, Carninci P, Tsuchizawa Y, Ishizu H, Siomi MC, Siomi H
  • Journal Title: Moleular Cell Volume: 59 Pages: 553-563
  • DOI: 10.1016/j.molcel.2015.06.024
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Somatic Primary piRNA Biogenesis Driven by cis-Acting RNA Elements and trans-Acting Yb. (2015)
  • Author(s): Ishizu H, Iwasaki YW, Hirakata S, Ozaki H, Iwasaki W, Siomi H, Siomi MC
  • Journal Title: Cell Reports. Volume: 12 Pages: 429-40
  • DOI: 10.1016/j.celrep.2015.06.035
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Respective functions of two distinct Siwi complexes assembled during PIWI-interacting RNA biogenesis in Bombyx germ cells (2015)
  • Author(s): Nishida, KM., Iwasaki, YW., Murota, Y., Nagao, A., Mannen, T., Kato, Y., Siomi, H., and Siomi, MC.
  • Journal Title: Cell reports Volume: 10 Pages: 193-203
  • DOI: 10.1016/j.celrep.2014.12.013
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] piRNA derived from ancient viral processed pseudogenes as transgenerational sequence-specific immune memory in mammals. (2015)
  • Author(s): Parrish NF, Fujino K, Shiromoto Y, Iwasaki YW, Ha H, Xing J, Makino A, Kuramochi-Miyagawa S, Nakano T, Siomi H, Honda T, Tomonaga K.
  • Journal Title: RNA Volume: 21 Pages: 1691-1703
  • DOI: 10.1261/rna.052092.115
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] PIWI-interacting RNA: Its biogenesis and functions. (2015)
  • Author(s): Iwasaki Y.W., Siomi M.C., Siomi H.
  • Journal Title: Annual Review of Biochem. Volume: 84 Pages: 405-433
  • DOI: 10.1146/annurev-biochem-060614-034258
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Tudor-domain containing proteins act to make the piRNA pathways more robust in Drosophila. (2015)
  • Author(s): Sato K, Iwasaki YW, Siomi H, Siomi MC
  • Journal Title: Fly (Austin) Volume: 9 Pages: 86-90
  • DOI: 10.1080/19336934.2015.1128599
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Germline specific regulation of transposable elements by small RNA (2018)
  • Author(s): Iwasaki YW
  • Organizer: Interdisciplinary Science Group in Keio
  • Invited
• [Presentation] Essential function of Panoramix/Silencio-Nxf2 complex in the Drosophila Piwi-piRNA pathway (2017)
  • Author(s): Iwasaki YW, Mashiko A, Murano K, Siomi H
  • Organizer: The 43rd Naito Conference: Noncoding RNA : Biology, Chemistry, & Diseases
  • Place of Presentation: シャトレーゼ ガトーキングダム サッポロ（札幌）
  • Year and Date: 2017-06-27
  • Int'l Joint Research
• [Presentation] Essential function of Panoramix/Silencio-Nxf2 complex in the Drosophila Piwi-piRNA pathway (2017)
  • Author(s): Iwasaki YW, Mahiko A, Murano K, Siomi H
  • Organizer: The 43rd Naito Conference: Noncoding RNA: Biology, Chemistry, and Disease
  • Int'l Joint Research
• [Presentation] Piwi-piRNAによるトランスポゾンの転写抑制機構 (2017)
  • Author(s): 岩崎由香
  • Organizer: NGS現場の会 第５回研究会
  • Invited
• [Presentation] 生殖組織特異的に発現する小分子RNAによる 転移因子の発現制御 (2017)
  • Author(s): 岩崎由香
  • Organizer: 10th Symphony
  • Invited
• [Presentation] Essential function of Panoramix/Silencio-Nxf2 complex in the Drosophila Piwi-piRNA pathway (2017)
  • Author(s): Murano K , Iwasaki YW , Mashiko A, Siomi H
  • Organizer: 第19回日本RNA学会年会
• [Presentation] Modulation of chromatin accessibility by Piwi results in transcriptional regulation (2016)
  • Author(s): Iwasaki YW, Murano K, Ishizu H, Shibuya A, Iyoda Y, Siomi MC, Siomi H, Saito K
  • Organizer: RNA2016: The 21st Annual Meeting of the RNA Society
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Functional analysis of CG9754/Panoramix/Silencio in the Drosophila Piwi-piRNA pathway (2016)
  • Author(s): Mashiko A, Iwasaki YW, Murano K, Siomi H
  • Organizer: RNA2016: The 21st Annual Meeting of the RNA Society
  • Place of Presentation: 国立京都国際会館（京都）
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Modulation of Chromatin Accessibility by Piwi Results in Transcriptional Regulation (2016)
  • Author(s): Iwasaki YW, Murano K, Ishizu H, Shibuya A, Iyoda Y, Siomi MC, Siomi H, Saito K
  • Organizer: RNA2016 The Joint Annual Meeting of the RNA Society and the RNA Society of Japan
  • Place of Presentation: 国立京都国際会館（京都府京都市）
  • Year and Date: 2016-06-28
  • Int'l Joint Research
• [Presentation] Piwi modulates chromatin accessibility for transcriptional regulation of transposons (2016)
  • Author(s): Iwasaki YW
  • Organizer: International Symposium “Clues to Non-coding RNA Taxonomy”
  • Place of Presentation: 東京大学弥生講堂一条ホール（東京）
  • Int'l Joint Research / Invited
• [Presentation] Piwi-piRNA complex regulates linker histone H1 for transcriptional silencing of their target transposons in the nucleus (2015)
  • Author(s): Iwasaki YW, Murano K, Ishizu H, Shibuya A, Iyoda Y, Siomi MC, Siomi H, Saito K
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] Piwi-piRNA promotes epigenetic silencing by regulating association of linker histone H1 with target transposon loci (2015)
  • Author(s): Iwasaki YW, Murano K, Ishizu H, Shibuya A, Iyoda Y, Siomi MC, Siomi H, Saito K
  • Organizer: The 40th Naito Conference on “Epigenetics; From Histone Code to Therapeutic Strategy”
  • Place of Presentation: シャトレーゼ ガトーキングタム（北海道札幌市）
  • Year and Date: 2015-09-15
  • Int'l Joint Research
• [Presentation] Piwi-piRNA regulates linker histone H1 for transcriptional silencing of their target transposable elements (2015)
  • Author(s): Iwasaki YW, Ishizu H, Shibuya A, Iyoda Y, Siomi MC, Siomi H, Saito K
  • Organizer: 日本RNA学会年会
  • Place of Presentation: ホテルライフォート札幌（北海道札幌市）
  • Year and Date: 2015-07-15
• [Presentation] Piwi-piRNA regulates association of linker histone H1 with target transposon loci in Drosophila (2015)
  • Author(s): Iwasaki YW, Ishizu H, Shibuya A, Iyoda Y, Siomi MC, Siomi H, Saito K
  • Organizer: RNA2015 The Twentieth Annual Meeting of the RNA Society
  • Place of Presentation: マディソン（アメリカ）
  • Year and Date: 2015-05-26
  • Int'l Joint Research