Contributed Terabiology: Understanding of biomolecular functions that utilize thermal fluctuations in the terahertz region - ICS84 The 84th Annual Meeting of the Israel Chemical Society

Masahiko Imashimizu ¹ Masahito Tanaka ² Hiromichi Hoshina ³ Koh Takeuchi ¹

¹Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Koto-ku, Tokyo, Japan
²Research Institute for Measurement and Analytical Instrumentation, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, Japan
³Terahertz Sensing and Imaging Research Team,, RIKEN Center for Advanced Photonics, Sendai, Miyagi, Japan

Thermally and actively driven fluctuations play a critical role in key cellular processes, such as DNA replication, transcription and translation, to mention just a few examples of the processes depending on protein-DNA interactions. Such fluctuations span a wide spectrum of length and time scales, ranging from angstroms to submicrons in space, and from subpicoseconds to milliseconds in time. For example, we have recently demonstrated that in the process of transcription, RNA polymerase (RNAP) pausing is regulated by thermal fluctuations that are modulated by RNAP interaction with DNA enriched in repetitive sequence elements (1,2). Aiming to experimentally elucidate molecular mechanism of this effect, transcription complexes consisting of RNAP, DNA and RNA in aqueous solution were irradiated by intense terahertz (THz) waves. The THz frequencies correspond to the energy range for the global biomolecular motions (of the order of 0.1-1 k_BT at room temperature), and thus may resonantly interact with specific vibrational modes of transcription complexes and surrounding water molecules. The effect of THz irradiation on transcription was statistically evaluated using a high-throughput DNA sequencing method. In particular, we found that transcription pausing and fidelity were significantly affected by the THz waves. However, since THz-heated water can also affect transcription by RNAP and stability of double-stranded DNA, we are currently identifying the origin of the THz-induced alternations in the biochemical processes observed in our experimental system.

Imashimizu M, Afek A, Takahashi H, Lubkowska L and Lukatsky DB, Control of transcriptional pausing by biased thermal fluctuations on repetitive genomic sequences, PNAS, 2016. 113 (47) E7409-17.
Imashimizu M and Lukatsky DB, Transcription pausing: biological significance of thermal fluctuations biased by repetitive genomic sequences, Transcription, 2018. 9(3): p.196-203.