Overall research goal of the Kirino lab is to understand the 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 transfer RNA (tRNA)-derived ncRNAs, cyclic phosphate-containing RNAs (cP-RNAs), and Piwi-interacting RNAs (piRNAs), which play crucial roles in various biological processes and diseases.

tRNA-derived ncRNAs in diseases: Since their discovery in the 1950s, tRNAs have been best known as abundant adapter components of the translational machinery, converting mRNA codon information into amino acid sequences. However, recent studies have established the new concept that tRNAs are further processed to generate specific tRNA-derived ncRNAs. We discovered that a novel type of tRNA-derived ncRNAs, termed Sex HOrmone-dependent TRNA-derived RNAs (SHOT-RNAs), are abundantly expressed in hormone-dependent breast and prostate cancers. SHOT-RNAs are produced from angiogenin-catalyzed anticodon cleavage of tRNAs and actively promote cell proliferation. Our studies have unveiled a novel tRNA-engaged pathway in tumorigenesis and implicate SHOT-RNAs as potential candidates for biomarkers and therapeutic targets in hormone-dependent cancers. While we have been continuously elucidating molecular mechanisms of SHOT-RNA function, we are further expanding our characterization of tRNA-derived ncRNAs in asthma and infectious diseases.

piRNA pathway in germline development: Piwi-interacting RNAs (piRNAs) are a germline-specific class of short ncRNAs that play crucial roles in germline development. We have been utilizing mouse, Bombyx, and Drosophila systems to elucidate the biogenesis mechanism of piRNAs. Piwi proteins, bound to piRNAs, contain a conserved arginine dimethylations, which are specifically recognized by Tudor domain of proteins. Our RNAi screening for Tudor proteins identified BmPapi as a novel piRNA biogenesis factor modulating piRNA maturation on mitochondrial outer membrane. The “Trimmer” enzyme responsible for piRNA 3′-end maturation has been identified by analyzing BmPapi-interacting proteins. Our studies further revealed how cell-cell contact regulates piRNA biogenesis and clarified how piRNAs are produced from tRNAs.

Novel tools for ncRNA sequencing and quantification: With the advent of next-generation sequencing, transcriptome profiling using RNA-seq has become a ubiquitous tool in biomedical research. However, standard RNA-seq method does not fully capture all of the cellular RNAs expressed; highly-structured or modified RNAs are often not efficiently sequenced by standard RNA-seq procedure. We have been developing methods for specific sequencing/quantification of those "difficult-to-analyze" RNAs to capture whole RNA expression profiles precisely

PhD, Integrated Biosciences, University of Tokyo - 2006
MSc, Integrated Biosciences, The University of Tokyo - 2003