Professor and Vice Chair for Research in the Department of Biochemistry and Molecular Biology; Professor in the Computational Medicine Center

Yohei Kirino

Professor and Vice Chair for Research in the Department of Biochemistry and Molecular Biology; Professor in the Computational Medicine Center

Short Bio

Dr. Kirino is a Professor in the Computational Medicine Center, and Professor and Vice Chair for Research in the Department of Biochemistry and Molecular Biology. Dr. Kirino joined Thomas Jefferson University (TJU) in mid-2013. The overall research goal of the Kirino lab is to understand biogenesis mechanism and molecular function of short non-coding RNAs (ncRNAs), and use the knowledge for development of novel biomarkers and therapeutic applications in diseases. Short ncRNAs have emerged as one of the most novel and exciting areas of gene expression regulation. By taking advantage of RNA biology/biochemistry, molecular/cellular biology, and computational biology, the Kirino lab is particularly focused on the two classes of short ncRNAs: Piwi-interacting RNAs (piRNAs) and transfer RNA (tRNA)-derived ncRNAs.

piRNAs are a germline-specific class of short ncRNAs which play crucial roles in germline development. The Kirino lab has been utilizing mouse, Bombyx, and Drosophila systems to elucidate the biogenesis mechanism of piRNAs. Recent studies of the lab identified BmPapi as a novel piRNA biogenesis factor (RNA 2013), revealed how cell-cell contact regulates piRNA biogenesis (Sci Rep 2017), and clarified how piRNAs are produced from tRNAs (Nucleic Acids Res 2017). The analyses of tRNA-derived piRNAs prompted them to expand their research efforts to study tRNA-derived ncRNAs in diseases. For the analyses of tRNAs and their fragments, the Kirino lab developed biochemical and sequencing tools: “Four-Leaf clover PCR” for quantification of tRNAs (RNA Biol 2015); “Dumbbell-PCR” for quantification of short RNA variants (Nucleic Acids Res 2016; Methods Mol Biol 2018); “cP-RNA-seq” for sequencing of cyclic-phosphate containing RNAs (Nat Protoc 2016); and “YAMAT-seq” for sequencing of tRNAs (Nucleic Acids Res 2017). Utilization of those methods lead to their recent discovery of a novel type of tRNA halves, termed SHOT-RNAs, which actively spur cell proliferation in hormone-dependent breast and prostate cancers (PNAS 2015). The study suggested a new role for tRNAs and tRNA-derived ncRNAs as a possible target for a new class of cancer therapy.

Prior to joining TJU, Dr. Kirino was Assistant Professor in Department of Biomedical Sciences at Cedars Sinai Medical Center (2010-2013) where he started his independent academic career. Dr. Kirino received his BSc (2001), MSc (2003) and PhD (2006) from The University of Tokyo (Dr. Tsutomu Suzuki’s lab) and performed Postdoc study (2006-2010) in University of Pennsylvania School of Medicine (Dr. Zissimos Mourelatos’ lab).

Publications

2024

  • Pawar, K, Kawamura, T, Kirino, Y. The tRNAVal half: A strong endogenous Toll-like receptor 7 ligand with a 5'-terminal universal sequence signature. Proc Natl Acad Sci U S A. 2024;121 (19):e2319569121. doi: 10.1073/pnas.2319569121. PubMed PMID:38683985.
  • Gumas, J, Kawamura, T, Shigematsu, M, Kirino, Y. Immunostimulatory short non-coding RNAs in the circulation of patients with tuberculosis infection. Mol Ther Nucleic Acids. 2024;35 (1):102156. doi: 10.1016/j.omtn.2024.102156. PubMed PMID:38481936 PubMed Central PMC10933579.

2022

  • Clemente, P, Calvo-Garrido, J, Pearce, SF, Schober, FA, Shigematsu, M, Siira, SJ, Laine, I, Spåhr, H, Steinmetzger, C, Petzold, K, Kirino, Y, Wibom, R, Rackham, O, Filipovska, A, Rorbach, J, Freyer, C, Wredenberg, A. ANGEL2 phosphatase activity is required for non-canonical mitochondrial RNA processing. Nat Commun. 2022;13 (1):5750. doi: 10.1038/s41467-022-33368-9. PubMed PMID:36180430 PubMed Central PMC9525292.
  • Shigematsu, M, Kirino, Y. Making Invisible RNA Visible: Discriminative Sequencing Methods for RNA Molecules with Specific Terminal Formations. Biomolecules. 2022;12 (5):. doi: 10.3390/biom12050611. PubMed PMID:35625540 PubMed Central PMC9138997.

2021

  • Shigematsu M, Kawamura T, Morichika K, Izumi N, Kiuchi T, Honda S, Pliatsika V, Matsubara R, Rigoutsos I, Katsuma S, Tomari Y, Kirino Y. RNase κ promotes robust piRNA production by generating 2',3'-cyclic phosphate-containing precursors. Nat Commun. 2021 Jul 23;12(1):4498. doi: 10.1038/s41467-021-24681-w. PubMed PMID:34301931.
  • Kawamura T, Shigematsu M, Kirino Y. In vitro production and multiplex quantification of 2',3'-cyclic phosphate-containing 5'-tRNA half molecules. Methods. 2021 May 4:S1046-2023(21)00124-9. doi: 10.1016/j.ymeth.2021.04.024. Epub ahead of print. PubMed PMID:33962012.

2020

  • Vrettos N, Maragkakis M, Alexiou P, Sgourdou P, Ibrahim F, Palmieri D, Kirino Y, Mourelatos Z. Modulation of Aub-TDRD interactions elucidates piRNA amplification and germplasm formation. Life Sci Alliance. 2020 Dec 29;4(3):e202000912. doi: 10.26508/lsa.202000912. PubMed PMID:33376130 PubMed Central PMCID:PMC7772777.
  • Pawar K, Shigematsu M, Sharbati S, Kirino Y. Infection-induced 5'-half molecules of tRNAHisGUG activate Toll-like receptor 7. PLoS Biol. 2020 Dec 17;18(12):e3000982. doi: 10.1371/journal.pbio.3000982. PubMed PMID:33332353.
  • Suzuki T, Yashiro Y, Kikuchi I, Ishigami Y, Saito H, Matsuzawa I, Okada S, Mito M, Iwasaki S, Ma D, Zhao X, Asano K, Lin H, Kirino Y, Sakaguchi Y, Suzuki T. Complete chemical structures of human mitochondrial tRNAs. Nat Commun. 2020 Aug 28;11(1):4269. doi: 10.1038/s41467-020-18068-6. PubMed PMID:32859890 PubMed Central PMC7455718.
  • Shigematsu, M, Kirino, Y. Oxidative stress enhances the expression of 2',3'-cyclic phosphate-containing RNAs. RNA Biol. 2020. doi: 10.1080/15476286.2020.1766861. PubMed PMID:32397797.

2019

  • Shigematsu, M, Morichika, K, Kawamura, T, Honda, S, Kirino, Y. Genome-wide identification of short 2',3'-cyclic phosphate-containing RNAs and their regulation in aging. PLoS Genet. 2019 Nov 13;15(11):e1008469. doi: 10.1371/journal.pgen.1008469. PubMed PMID:31721758.
  • Pawar, K, Shigematsu, M, Loher, P, Honda, S, Rigoutsos, I, Kirino, Y. Exploration of CCA-added RNAs revealed the expression of mitochondrial non-coding RNAs regulated by CCA-adding enzyme. RNA Biol. 2019 Sep 12:1-9. doi: 10.1080/15476286.2019.1664885. PubMed PMID:31512554.
  • Rigoutsos, I, Londin, E, Kirino, Y. Short RNA regulators: the past, the present, the future, and implications for precision medicine and health disparities. Curr Opin Biotechnol. 2019 Aug;58:202-210. doi: 10.1016/j.copbio.2019.05.014. PubMed PMID:31323485.
  • Telonis, AG, Loher, P, Magee, R, Pliatsika, V, Londin, E, Kirino, Y, Rigoutsos, I. tRNA Fragments Show Intertwining with mRNAs of Specific Repeat Content and Have Links to Disparities. Cancer Res. 2019 Apr 17. doi: 10.1158/0008-5472.CAN-19-0789. PubMed PMID:30996049.

2018

  • Shigematsu, M, Kawamura, T, Kirino, Y. Generation of 2',3'-Cyclic Phosphate-Containing RNAs as a Hidden Layer of the Transcriptome. Front Genet. 2018;9 :562. doi: 10.3389/fgene.2018.00562. PubMed PMID:30538719 PubMed Central PMC6277466.
  • Pliatsika, V, Loher, P, Magee, R, Telonis, AG, Londin, E, Shigematsu, M, Kirino, Y, Rigoutsos, I. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects. Nucleic Acids Res. 2018;46 (D1):D152-D159. doi: 10.1093/nar/gkx1075. PubMed PMID:29186503 PubMed Central PMC5753276.
  • Shigematsu, M, Honda, S, Kirino, Y. Dumbbell-PCR for Discriminative Quantification of a Small RNA Variant. Methods Mol. Biol. 2018;1680 :65-73. doi: 10.1007/978-1-4939-7339-2_4. PubMed PMID:29030841.

2017

  • Shigematsu, M, Kirino, Y. 5"-Terminal nucleotide variations in human cytoplasmic tRNAHisGUG and its 5"-halves. RNA. 2017;23 (2):161-168. doi: 10.1261/rna.058024.116. PubMed PMID:27879434 PubMed Central PMC5238791.
  • Honda, S, Loher, P, Morichika, K, Shigematsu, M, Kawamura, T, Kirino, Y, Rigoutsos, I, Kirino, Y. Increasing cell density globally enhances the biogenesis of Piwi-interacting RNAs in Bombyx mori germ cells. Sci Rep. 2017;7 (1):4110. doi: 10.1038/s41598-017-04429-7. PubMed PMID:28646211 PubMed Central PMC5482885.
  • Honda, S, Kawamura, T, Loher, P, Morichika, K, Rigoutsos, I, Kirino, Y. The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells. Nucleic Acids Res. 2017;45 (15):9108-9120. doi: 10.1093/nar/gkx537. PubMed PMID:28645172 PubMed Central PMC5587776.
  • Shigematsu, M, Honda, S, Loher, P, Telonis, AG, Rigoutsos, I, Kirino, Y. YAMAT-seq: an efficient method for high-throughput sequencing of mature transfer RNAs. Nucleic Acids Res. 2017;45 (9):e70. doi: 10.1093/nar/gkx005. PubMed PMID:28108659 PubMed Central PMC5605243.

2016

  • Telonis, AG, Loher, P, Kirino, Y, Rigoutsos, I. Consequential considerations when mapping tRNA fragments. BMC Bioinformatics. 2016;17 :123. doi: 10.1186/s12859-016-0921-0. PubMed PMID:26961774 PubMed Central PMC4785646.
  • Izumi, N, Shoji, K, Sakaguchi, Y, Honda, S, Kirino, Y, Suzuki, T, Katsuma, S, Tomari, Y. Identification and Functional Analysis of the Pre-piRNA 3" Trimmer in Silkworms. Cell. 2016;164 (5):962-73. doi: 10.1016/j.cell.2016.01.008. PubMed PMID:26919431 PubMed Central PMC4856147.
  • Honda, S, Morichika, K, Kirino, Y. Selective amplification and sequencing of cyclic phosphate-containing RNAs by the cP-RNA-seq method. Nat Protoc. 2016;11 (3):476-89. doi: 10.1038/nprot.2016.025. PubMed PMID:26866791 PubMed Central PMC4852555.
  • Sakai, H, Kirino, Y, Kastuma, S, Aoki, F, Suzuki, MG. Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori. Journal of Insect Biotechnology and Sericology 2016; 85: 15-20
  • Shigematsu, M, Kirino, Y. tRNA-Derived Short Non-coding RNA as Interacting Partners of Argonaute Proteins. Gene Regul Syst Bio. 2015;9 :27-33. doi: 10.4137/GRSB.S29411. PubMed PMID:26401098 PubMed Central PMC4567038.

2015

  • Telonis, AG, Loher, P, Honda, S, Jing, Y, Palazzo, J, Kirino, Y, Rigoutsos, I. Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. Oncotarget. 2015;6 (28):24797-822. doi: 10.18632/oncotarget.4695. PubMed PMID:26325506 PubMed Central PMC4694795.
  • Honda, S, Loher, P, Shigematsu, M, Palazzo, JP, Suzuki, R, Imoto, I, Rigoutsos, I, Kirino, Y. Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers. Proc. Natl. Acad. Sci. U.S.A. 2015;112 (29):E3816-25. doi: 10.1073/pnas.1510077112. PubMed PMID:26124144 PubMed Central PMC4517238.
  • Telonis, AG, Kirino, Y, Rigoutsos, I. Mitochondrial tRNA-lookalikes in nuclear chromosomes: could they be functional?. RNA Biol. 2015;12 (4):375-80. doi: 10.1080/15476286.2015.1017239. PubMed PMID:25849196 PubMed Central PMC4615777.
  • Honda, S, Shigematsu, M, Morichika, K, Telonis, AG, Kirino, Y. Four-leaf clover qRT-PCR: A convenient method for selective quantification of mature tRNA. RNA Biol. 2015;12 (5):501-8. doi: 10.1080/15476286.2015.1031951. PubMed PMID:25833336 PubMed Central PMC4615770.
  • Honda, S, Kirino, Y. Dumbbell-PCR: a method to quantify specific small RNA variants with a single nucleotide resolution at terminal sequences. Nucleic Acids Res. 2015;43 (12):e77. doi: 10.1093/nar/gkv218. PubMed PMID:25779041 PubMed Central PMC4499115.
  • Londin, E, Loher, P, Telonis, AG, Quann, K, Clark, P, Jing, Y, Hatzimichael, E, Kirino, Y, Honda, S, Lally, M, Ramratnam, B, Comstock, CE, Knudsen, KE, Gomella, L, Spaeth, GL, Hark, L, Katz, LJ, Witkiewicz, A, Rostami, A, Jimenez, SA, Hollingsworth, MA, Yeh, JJ, Shaw, CA, McKenzie, SE, Bray, P, Nelson, PT, Zupo, S, Van Roosbroeck, K, Keating, MJ, Calin, GA, Yeo, C, Jimbo, M, Cozzitorto, J, Brody, JR, Delgrosso, K, Mattick, JS, Fortina, P, Rigoutsos, I. Analysis of 13 cell types reveals evidence for the expression of numerous novel primate- and tissue-specific microRNAs. Proc. Natl. Acad. Sci. U.S.A. 2015;112 (10):E1106-15. doi: 10.1073/pnas.1420955112. PubMed PMID:25713380 PubMed Central PMC4364231.

2014

  • Honda, S, Kirino, Y. SHOT-RNAs: a novel class of tRNA-derived functional RNAs expressed in hormone-dependent cancers. Molecular & Cellular Oncology. 2015;3:2. doi: 10.1080/23723556.2015.1079672.
  • Telonis, AG, Loher, P, Kirino, Y, Rigoutsos, I. Nuclear and mitochondrial tRNA-lookalikes in the human genome. Front Genet. 2014;5 :344. doi: 10.3389/fgene.2014.00344. PubMed PMID:25339973 PubMed Central PMC4189335.
  • Honda, S, Kirino, Y, Kirino, Y. Analysis of sDMA modifications of PIWI proteins. Methods Mol. Biol. 2014;1093 :137-48. doi: 10.1007/978-1-62703-694-8_11. PubMed PMID:24178562 PubMed Central PMC4376280.
  • Shigematsu, M, Honda, S, Kirino, Y (2014) "Transfer RNA as a Source of Small Functional RNA"J Mol Biol & Mol Imaging 1(2): 8 doi: Download
  • Honda, S, Kirino, Y, Maragkakis, M, Alexiou, P, Ohtaki, A, Murali, R, Mourelatos, Z, Kirino, Y. Mitochondrial protein BmPAPI modulates the length of mature piRNAs. RNA. 2013;19 (10):1405-18. doi: 10.1261/rna.040428.113. PubMed PMID:23970546 PubMed Central PMC3854531.

2013

  • Honda, S and Kirino, Y (2013) “PIWIL1 (piwi-like RNA-mediated gene silencing 1)” Atlas Genet Cytogenet Oncol Haematol. 17(12):833-836. doi: Genes/PIWIL1ID46561ch12q24

2012

  • Suzuki, R, Honda, S, Kirino, Y. PIWI Expression and Function in Cancer. Front Genet. 2012;3 :204. doi: 10.3389/fgene.2012.00204. PubMed PMID:23087701 PubMed Central PMC3472457.
  • Vourekas, A, Zheng, Q, Alexiou, P, Maragkakis, M, Kirino, Y, Gregory, BD, Mourelatos, Z. Mili and Miwi target RNA repertoire reveals piRNA biogenesis and function of Miwi in spermiogenesis. Nat. Struct. Mol. Biol. 2012;19 (8):773-81. doi: 10.1038/nsmb.2347. PubMed PMID:22842725 PubMed Central PMC3414646.

2011

  • Kirino, Y. [Role of arginine methylation in the Piwi-interacting RNA pathway]. Seikagaku. 2011;83 (4):312-6.. PubMed PMID:21626884.
  • Kirino, Y, Vourekas, A, Khandros, E, Mourelatos, Z. Immunoprecipitation of piRNPs and directional, next generation sequencing of piRNAs. Methods Mol. Biol. 2011;725 :281-93. doi: 10.1007/978-1-61779-046-1_18. PubMed PMID:21528460.

2010

  • Mimaki, M, Hatakeyama, H, Komaki, H, Yokoyama, M, Arai, H, Kirino, Y, Suzuki, T, Nishino, I, Nonaka, I, Goto, Y. Reversible infantile respiratory chain deficiency: a clinical and molecular study. Ann. Neurol. 2010;68 (6):845-54. doi: 10.1002/ana.22111. PubMed PMID:21194154.
  • Vourekas, A, Kirino, Y, Mourelatos, Z. Elective affinities: a Tudor-Aubergine tale of germline partnership. Genes Dev. 2010;24 (18):1963-6. doi: 10.1101/gad.1977010. PubMed PMID:20844011 PubMed Central PMC2939360.
  • Kirino, Y, Vourekas, A, Kim, N, de Lima Alves, F, Rappsilber, J, Klein, PS, Jongens, TA, Mourelatos, Z. Arginine methylation of vasa protein is conserved across phyla. J. Biol. Chem. 2010;285 (11):8148-54. doi: 10.1074/jbc.M109.089821. PubMed PMID:20080973 PubMed Central PMC2832966.
  • Kirino, Y, Vourekas, A, Sayed, N, de Lima Alves, F, Thomson, T, Lasko, P, Rappsilber, J, Jongens, TA, Mourelatos, Z. Arginine methylation of Aubergine mediates Tudor binding and germ plasm localization. RNA. 2010;16 (1):70-8. doi: 10.1261/rna.1869710. PubMed PMID:19926723 PubMed Central PMC2802038.

2009

  • Kirino, Y, Kim, N, de Planell-Saguer, M, Khandros, E, Chiorean, S, Klein, PS, Rigoutsos, I, Jongens, TA, Mourelatos, Z. Arginine methylation of Piwi proteins catalysed by dPRMT5 is required for Ago3 and Aub stability. Nat. Cell Biol. 2009;11 (5):652-8. doi: 10.1038/ncb1872. PubMed PMID:19377467 PubMed Central PMC2746449.

2008

  • Kirino, Y, Mourelatos, Z. Site-specific crosslinking of human microRNPs to RNA targets. RNA. 2008;14 (10):2254-9. doi: 10.1261/rna.1133808. PubMed PMID:18719246 PubMed Central PMC2553735.
  • Kurata, S, Weixlbaumer, A, Ohtsuki, T, Shimazaki, T, Wada, T, Kirino, Y, Takai, K, Watanabe, K, Ramakrishnan, V, Suzuki, T. Modified uridines with C5-methylene substituents at the first position of the tRNA anticodon stabilize U.G wobble pairing during decoding. J. Biol. Chem. 2008;283 (27):18801-11. doi: 10.1074/jbc.M800233200. PubMed PMID:18456657.

2007

  • Kirino, Y, Mourelatos, Z. 2"-O-methyl modification in mouse piRNAs and its methylase. Nucleic Acids Symp Ser (Oxf). 2007; (51):417-8. doi: 10.1093/nass/nrm209. PubMed PMID:18029764.
  • Kirino, Y, Mourelatos, Z. The mouse homolog of HEN1 is a potential methylase for Piwi-interacting RNAs. RNA. 2007;13 (9):1397-401. doi: 10.1261/rna.659307. PubMed PMID:17652135 PubMed Central PMC1950760.
  • Kirino, Y, Mourelatos, Z. Mouse Piwi-interacting RNAs are 2"-O-methylated at their 3" termini. Nat. Struct. Mol. Biol. 2007;14 (4):347-8. doi: 10.1038/nsmb1218. PubMed PMID:17384647.

2006

  • Noma, A, Kirino, Y, Ikeuchi, Y, Suzuki, T. Biosynthesis of wybutosine, a hyper-modified nucleoside in eukaryotic phenylalanine tRNA. EMBO J. 2006;25 (10):2142-54. doi: 10.1038/sj.emboj.7601105. PubMed PMID:16642040 PubMed Central PMC1462984.
  • Kirino, Y, Yasukawa, T, Marjavaara, SK, Jacobs, HT, Holt, IJ, Watanabe, K, Suzuki, T. Acquisition of the wobble modification in mitochondrial tRNALeu(CUN) bearing the G12300A mutation suppresses the MELAS molecular defect. Hum. Mol. Genet. 2006;15 (6):897-904. doi: 10.1093/hmg/ddl007. PubMed PMID:16446307.

2005

  • Kirino, Y, Suzuki, T. Human mitochondrial diseases associated with tRNA wobble modification deficiency. RNA Biol. 2005;2 (2):41-4.. PubMed PMID:17132941.
  • Yasukawa, T, Kirino, Y, Ishii, N, Holt, IJ, Jacobs, HT, Makifuchi, T, Fukuhara, N, Ohta, S, Suzuki, T, Watanabe, K. Wobble modification deficiency in mutant tRNAs in patients with mitochondrial diseases. FEBS Lett. 2005;579 (13):2948-52. doi: 10.1016/j.febslet.2005.04.038. PubMed PMID:15893315.
  • Kirino, Y, Goto, Y, Campos, Y, Arenas, J, Suzuki, T. Specific correlation between the wobble modification deficiency in mutant tRNAs and the clinical features of a human mitochondrial disease. Proc. Natl. Acad. Sci. U.S.A. 2005;102 (20):7127-32. doi: 10.1073/pnas.0500563102. PubMed PMID:15870203 PubMed Central PMC1129107.
  • Kirino, Y. and Suzuki, T (2005) "MELAS A3243G mutation and tRNA modification disorder" Rinsyoukensa 49: 89-95

2004

  • Kirino, Y, Yasukawa, T, Ohta, S, Akira, S, Ishihara, K, Watanabe, K, Suzuki, T. Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease. Proc. Natl. Acad. Sci. U.S.A. 2004;101 (42):15070-5. doi: 10.1073/pnas.0405173101. PubMed PMID:15477592 PubMed Central PMC524061.
  • Limongelli, A, Schaefer, J, Jackson, S, Invernizzi, F, Kirino, Y, Suzuki, T, Reichmann, H, Zeviani, M. Variable penetrance of a familial progressive necrotising encephalopathy due to a novel tRNA(Ile) homoplasmic mutation in the mitochondrial genome. J. Med. Genet. 2004;41 (5):342-9.. PubMed PMID:15121771 PubMed Central PMC1735786.

2003

  • Kurata, S, Ohtsuki, T, Wada, T, Kirino, Y, Takai, K, Saigo, K, Watanabe, K, Suzuki, T. Decoding property of C5 uridine modification at the wobble position of tRNA anticodon. Nucleic Acids Res. Suppl. 2003; (3):245-6.. PubMed PMID:14510472.

Contact Info

Email: Yohei.Kirino@jefferson.edu