TY - JOUR T1 - Unifying Gene Expression Complexity and Cellular Operational Efficiency: Application of the Locality and Caching Principles via a Cell-to-Computer Analogy JF - bioRxiv DO - 10.1101/2022.01.11.475967 SP - 2022.01.11.475967 AU - Wen Jiang AU - Denis Feliers AU - W. Jim Zheng AU - Fangyuan Zhang AU - Degeng Wang Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/01/13/2022.01.11.475967.abstract N2 - Gene expression is time-consuming, and the delay from transcription activation to produced proteins is sequentially longer from bacteria to yeast and to humans. How human cells bypass the delay and attain operational efficiency, i.e., quick proteomic response to signals, is not well understood. The computer has endured the same system latency issue due to much slower information retrieval (hard drive (HD) to memory and to CPU) than CPU execution, and mitigated it via efficient memory management, namely, the spatiotemporal locality principles that control specialized user functions and the permanent caching of core system functions – the operating system (OS) kernel. Thus, in this study, we unified gene expression and HD-memory-CPU information flow as instances of the Shannon information theory, both supporting the respective system operations and consisting of three components: information storage, the execution/decoding step, and the channel for the dynamic storage-to-execution information flow; the gene expression machinery and their regulators, and the OS kernel, were deemed as the respective channels. This abstraction prompted a multi-omic comparative analysis, generating experimental evidence that transcriptome regulation shares the computer memory management principles. First, the temporal locality principle explains the mRNA stabilization-by-translation regulatory mechanism and controls specialized cellular functions. Second, the caching principle explains cytoplasmic mRNA sequestration and the defiance of the locality principle by highly sequestered mRNAs. Third, strikingly, in both systems, the caching principle controls the information channels; similar to permanent caching of OS kernel, basic translation/transcription machinery and their regulators are the top most sequestered mRNAs. Summarily, the locality and the caching principles differentially regulate specialized functions and core system functions, respectively, integrating the complexity of transcriptome regulation with cellular operational latency mitigation.Competing Interest StatementThe authors have declared no competing interest. ER -