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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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A Reporter Based Cellular Assay for Monitoring Splicing Efficiency
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Frequency analysis of splicing regulation.

Alberto Giaretta

    Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
    |December 11, 2021
    PubMed
    Summary

    This study introduces frequency domain analysis for gene networks with post-transcriptional splicing regulation. It reveals how burst size, splicing rates, and feedback control influence system dynamics and noise.

    Area of Science:

    • Systems Biology
    • Computational Biology
    • Molecular Biology

    Background:

    • Existing gene network models primarily focus on transcriptional and translational regulation.
    • Mathematical frameworks for post-transcriptional splicing regulation, especially its integration with other regulatory layers, are underdeveloped.
    • Current research on splicing regulation is limited to steady-state analysis, neglecting frequency domain dynamics.

    Purpose of the Study:

    • To theoretically investigate a gene network with splicing regulation using a frequency domain approach.
    • To analyze the impact of negative feedback control on splicing-regulated gene networks.
    • To explore the dynamical response of gene networks in the frequency domain.

    Main Methods:

    • Development of mathematical models for gene networks incorporating post-transcriptional splicing.

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  • Frequency domain analysis to study system dynamics and noise.
  • Investigation of systems with and without negative feedback control.

    • Main Results:

    • Identified the critical role of burst size and splicing conversion rates in modulating noise and power spectrum response.
    • Demonstrated that these parameters significantly influence the frequency domain behavior of gene networks.
    • Observed unique dynamical behaviors arising from the interplay of burst size, splicing rates, and negative feedback strength.

    Conclusions:

    • Post-transcriptional splicing regulation significantly impacts gene network dynamics.
    • Frequency domain analysis provides a more comprehensive understanding of gene network behavior than steady-state analysis.
    • Burst size, splicing rates, and feedback mechanisms are key modulators of gene expression noise and frequency response.