Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (3 results)

  • Thesis
  • Peer Reviewed
UC Davis Electronic Theses and Dissertations (2023)

Eukaryotic gene expression is compartmentalized with transcription of genetic information from DNA into messenger RNA (mRNA) occurring in the nucleus and translation of these messages into proteins occurring in the cytoplasm. These cellular processes are physically separated by the nuclear envelope, a double membrane system that prevents exchange of macromolecules between nuclear and cytoplasmic compartments. RNA and proteins are not able to passively diffuse across this barrier but rather require transport receptors to facilitate docking and transit in and out of the nucleus through Nuclear Pore Complexes (NPCs). A GTP driven process that requires the small Ras like GTPase Ran to regulate nucleocytoplasmic shuttling of cargo is traditionally thought to regulate non-coding RNA (ncRNA) localization. Meanwhile mRNA export is regulated by the heterodimeric transport receptor Mex67-Mtr2 (Tap-p15/NXF1-NXT1 in humans) and ATP via the activity of the DEAD box Protein 5 (Dbp5 in yeast, DDX19 in humans), which is not directly dependent on Ran function. The work presented here describes how Dbp5 also regulates ncRNA export, revealing a novel ATP driven ncRNA export pathway and broader functions of mRNA export factors Dbp5 and Mex67 as general RNA export adapters.

    Cover page: Investigating a Role for the DEAD-box Protein 5 (Dbp5) in tRNA Regulation
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2021)
    The DEAD-box protein (DBP) Dbp5, a member of the superfamily II (SFII) helicases, has multiple reported roles in gene expression. First identified as an essential regulator of mRNA export in Saccharomyces cerevisiae, the enzyme now has reported functions in non-coding RNA export, translation, transcription, and DNA metabolism. Localization of the protein to various cellular compartments (nucleoplasm, nuclear envelope, and cytoplasm) highlights the ability of Dbp5 to modulate different stages of the RNA lifecycle. While Dbp5 has been well studied for > 20 years, several critical questions remain regarding the mechanistic principles that govern Dbp5 localization, substrate selection, and functions in gene expression. This review aims to take a holistic view of the proposed functions of Dbp5 and evaluate models that accommodate current published data.
      Cover page: Emerging molecular functions and novel roles for the DEAD-box protein Dbp5/DDX19 in gene expression
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2020)
      RNA-binding proteins (RBPs) are key mediators of RNA metabolism. Whereas some RBPs exhibit narrow transcript specificity, others function broadly across both coding and non-coding RNAs. Here, in Saccharomyces cerevisiae, we demonstrate that changes in RBP availability caused by disruptions to distinct cellular processes promote a common global breakdown in RNA metabolism and nuclear RNA homeostasis. Our data shows that stabilization of aberrant ribosomal RNA (rRNA) precursors in an enp1-1 mutant causes phenotypes similar to RNA exosome mutants due to nucleolar sequestration of the poly(A)-binding protein (PABP) Nab2. Decreased nuclear PABP availability is accompanied by genome-wide changes in RNA metabolism, including increased pervasive transcripts levels and snoRNA processing defects. These phenotypes are mitigated by overexpression of PABPs, inhibition of rDNA transcription, or alterations in TRAMP activity. Our results highlight the need for cells to maintain poly(A)-RNA levels in balance with PABPs and other RBPs with mutable substrate specificity across nucleoplasmic and nucleolar RNA processes.
        Cover page: Altered rRNA processing disrupts nuclear RNA homeostasis via competition for the poly(A)-binding protein Nab2
        Top