Emerging molecular functions and novel roles for the DEAD-box protein Dbp5/DDX19 in gene expression
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Cellular and Molecular Life Sciences
REVIEW
Emerging molecular functions and novel roles for the DEAD‑box protein Dbp5/DDX19 in gene expression Arvind Arul Nambi Rajan1 · Ben Montpetit1,2 Received: 18 July 2020 / Revised: 21 September 2020 / Accepted: 6 October 2020 © Springer Nature Switzerland AG 2020
Abstract 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. Keywords DBP5 · DDX19 · GLE1 · NUP159 · Nuclear pore complex · mRNA export · Gene expression · mRNP · RNPase
Introduction DEAD-box proteins (DBPs) function ubiquitously throughout the process of gene expression [1, 2]. With 25 of these enzymes identified in yeast and > 35 in humans, they represent the largest group amongst SFII helicases [1, 3]. Generally, DBPs are composed of two RecA-like domains, containing several critical helicase motifs (Q and motif I–VI), which are connected by a flexible linker region (Fig. 1a). This includes the namesake Asp-Glu-Ala-Asp (D-E-A-D) motif contained within motif II. Together these motifs allow DBPs to recognize and hydrolyze ATP, bind nucleic acids, and invoke structural rearrangements on nucleic acid substrates. The highly conserved architecture of DEAD-box proteins has aided scientists in understanding the mechanistic properties governing these ATPases and the diverse processes they engage through common modes of action (refer to Fig. 1b). This includes facilitating formation of * Ben Montpetit [email protected] 1
Biochemistry, Molecular, Cellular and Developmental Biology Graduate Group, University of California Davis, Davis, CA, USA
Department of Viticulture and Enology, University of California Davis, Davis, CA, USA
2
ribonucleoprotein (RNP) complexes by acting as a stably bound component (mode 1), using an “RNPase activity” to remodel the structure of RNPs by displacing bound proteins (mode 2), or RNA duplex unwinding (mode 3). Two DBPs, Sub2 and Dbp5, have been linked specifically to the essential process of messenger RNA (mRNA) export from the nucleus [4–6]. As a component of the TRanscription-EXport (TREX) complex, Sub2 (UAP56 in humans) serves an important role in assembly of the nuclear export competent mRNP [3, 4]. For example, during mRNA transcription, nuclear “export receptors” (e.g., Me
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