TOMOKO TAKAHASHI
LAB

About us

Molecular Principles and Control of Cell State–Dependent Selection of Exogenous RNA Responses

In living systems, the same stimulus can elicit entirely different responses depending on the type and state of the cell. This diversity and selectivity of cellular responses form the foundation of biological flexibility and adaptability; however, the underlying molecular principles remain incompletely understood.

In particular, cellular responses to exogenous RNAs—such as those introduced during viral infection or through nucleic acid therapeutics—diverge into multiple outcomes, including RNA degradation, translational repression, interferon responses, and cell death. Despite extensive studies on these individual pathways, a fundamental question remains unanswered:

Why do identical exogenous RNAs trigger markedly different responses depending on the cellular state?

To address this question, our research focuses on the interplay among exogenous RNAs, endogenous RNAs, and RNA-binding proteins. We propose that cellular responses to exogenous RNA are not determined solely by the intrinsic properties of the RNA itself, but rather by the state of the intracellular RNA network formed by endogenous RNAs and RNA-binding factors.

By viewing exogenous RNA responses not as isolated molecular pathways but as dynamic changes in RNA network architecture, we aim to establish a unified framework that integrates phenomena traditionally studied separately—such as RNA degradation, interferon responses, and apoptosis—into a coordinated system of response selection.

Ultimately, our goal is to provide a unified understanding of seemingly distinct biological processes, including viral infection, cancer, and responses to nucleic acid therapeutics. More broadly, we aim to uncover general principles by which cells select appropriate responses to diverse stimuli.

Selected Research Topics

⚫︎ Impact of the exogenous RNA sensor on endogenous RNA regulatory systems
　 Takahashi et al. 2020 NAR, Takahashi et al. 2018 NAR

⚫︎ Functional modulation of the RNA-binding protein TRBP upon exogenous RNA introduction
　 Shibata and Moriizumi et al 2024 NAR

⚫︎ Computational analysis of interactions between endogenous and exogenous RNAs
　 Shibamoto and Kitsu et al 2024 Biol. Open

⚫︎ Review on small RNA–mediated antiviral immune systems
　 Takahashi et al. 2021 PLoS Pathog.

⚫︎ Molecular design of small nucleic acids such as siRNAs
　 Takahashi et al. 2014 NAR

For further details on our ongoing research, please feel free to contact Tomoko Takahashi.