A glimpse at mRNA dynamics reveals cellular domains and rapid trafficking through granules

Gemert, A.M.C. van (2011)

Doctoral Thesis

mRNA transport and targeting are essential to gene expression regulation. Specific mRNA sequences can bind several proteins and together form RiboNucleoProtein particles (RNP). The various proteins within the RNP determine mRNA fate: translation, transport or decay. RNP composition varies with localization, cell cycle and environmental cues. RNPs can move freely throughout the cytoplasm or bind subcellular cell structures depending on the contained mRNA. RNPs are associated with ribosomes when the mRNAs need to be translated, with transport granules if the mRNAs are targeted to a specific cellular location or with Processing Bodies (PB) or Stress Granules (SG) if translation needs to be turned down or the mRNAs are to be degraded. Insight into the mechanisms dictating RNP transition from one state to the other will lead to improved understanding of gene regulation itself. Therefore, this thesis aimed at investigating mRNA dynamics. Most experiments were performed in Drosophila embryonic muscles as they can be visualized in the whole living organism placed on a microscope stage, thus approaching endogenous conditions. Besides, several strategies involving gene or cell therapies to treat myopathies are being developed, implying that therapeutic mRNAs have the ability to move throughout the entire myoplasm. This was another reason for using muscle cells in most of our experiments.

• Drosophila
• FRAP
• Microscopy
• mRNA
• Molecular cell biology

• All authors: Gemert, A.M.C. van
• Supervisor: Tanke, H.J.
• Co-supervisor: Jost, C.R.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2011-09-21