Yohei Kirino, PhD

The overarching goal of the Kirino lab is to decode how short non-coding RNAs (sncRNAs) are created, how they move and signal within and between cells, and how this hidden layer of the transcriptome can be exploited for diagnostics and therapeutics. Over the past two decades, work from our group and others has revealed sncRNAs as pivotal regulators at the crossroads of gene expression, stress responses, innate immunity, and beyond. By integrating RNA biology/biochemistry, molecular and cellular biology, and sequencing/computational approaches, the Kirino lab focuses on transfer RNA (tRNA)-derived sncRNAs (particularly tRNA halves), cyclic phosphate–containing RNAs (cP-RNAs), and Piwi-interacting RNAs (piRNAs) in human disease and development.

Hormone-dependent tRNA halves in cancer growth and progression
The lab has identified sex hormone–dependent tRNA halves that are abundantly expressed in hormone-dependent breast and prostate cancers. Generated by angiogenin-catalyzed anticodon cleavage, these tRNA halves actively promote tumor cell proliferation, revealing a tRNA half-driven pathway in tumorigenesis and positioning them as candidate biomarkers and RNA-based targets in hormone-dependent malignancies.

Immunostimulatory tRNA halves in infection, lung disease, and neuropsychiatric disorders
The lab has uncovered disease-induced tRNA halves that function as potent innate immune ligands. We identified infection-induced tRNA halves in human macrophages that are selectively packaged into extracellular vesicles and activate endosomal Toll-like receptor 7 (TLR7), with marked upregulation in plasma from patients with Mycobacterium tuberculosis infection. We further showed that specific tRNA halves elevated in chronic obstructive pulmonary disease (COPD) plasma activate human macrophages via TLR7 and induce cytokine production, establishing circulating tRNA halves as immune mediators in chronic lung disease. Ongoing and collaborative work extends these studies to eosinophil-derived neurotoxin (RNase 2/EDN)-mediated production of tRNA halves in asthma, and to dysregulated tRNA halves in schizophrenia. Together, these findings define tRNA halves as a previously unrecognized class of endogenous immunostimulants and position them as candidate targets and tools for next-generation RNA-based therapies.

Circulating sncRNAs and next-generation platforms for hidden RNA biomarker profiling
Because many structured/modified sncRNAs escape standard RNA-seq, the lab has developed specialized platforms such as cP-RNA-seq for cP-RNAs (including 5′-tRNA halves), YAMAT-seq for mature tRNAs, and highly sensitive assays including Dumbbell-PCR, Four-Leaf Clover RT-qPCR, and multiplex TaqMan RT-qPCR. These tools allow us to profile otherwise hidden sncRNAs in cells and clinical biofluids, generating genome-wide maps of cP-RNAs, revealing previously unrecognized mitochondrial sncRNAs, and defining disease-specific signatures of tRNA- and rRNA-derived sncRNAs, where circulating sncRNAs behave as liquid-biopsy biomarkers and active immunomodulators. By applying this technology suite in collaborative studies, we aim to establish sncRNA-based biomarker panels and identify new RNA-targeted therapeutic entry points.

piRNA biogenesis and germline genome defense
piRNAs are germline-specific sncRNAs essential for transposon silencing and fertility. Using mouse and Bombyx models, the lab has identified key factors in piRNA biogenesis, including the Tudor-domain protein BmPapi, which scaffolds piRNA maturation on mitochondria, and the mitochondria-associated endoribonuclease RNase κ, which produces cP-RNAs as direct piRNA precursors and thereby establishes cP-RNAs as central intermediates linking RNA metabolism, piRNA biogenesis, and germline development.

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

• Dr. Kirino's Research Lab Site