RNA helicase proteins as chaperones and remodelers

Abstract

Superfamily 2 helicase proteins are ubiquitous in RNA biology and have an extraordinarily broad set of functional roles. Central among these roles are the promotion of rearrangements of structured RNAs and the remodeling of ribonucleoprotein complexes (RNPs), allowing formation of native RNA structure or progression through a functional cycle of structures. Although all superfamily 2 helicases share a conserved helicase core, they are divided evolutionarily into several families, and it is principally proteins from three families, the DEAD-box, DEAH/RHA, and Ski2-like families, that function to manipulate structured RNAs and RNPs. Strikingly, there are emerging differences in the mechanisms of these proteins, both between families and within the largest family (DEAD-box), and these differences appear to be tuned to their RNA or RNP substrates and their specific roles. This review outlines basic mechanistic features of the three families and surveys individual proteins and the current understanding of their biological substrates and mechanisms.

Keywords: ATPase; RNA folding; RNA structure; RNA unwinding; self-splicing intron.

Figure 1. SF2 families involved in RNA chaperoning and RNP remodeling

(a) Arrangement of conserved structural domains. Conserved motifs of the helicase core are shown in dark gray. The domain arrangements of DEAH/RHA and Ski2-like families shown are based on Mtr4 and Prp43 structures, respectively (domains not to scale). The winged helix and ratchet domains are conserved in DEAH/RHA and Ski2-like helicases and the OB fold domain is conserved in DEAH/RHA helicases, while the arch domain is present in only a subset of Ski2-like helicases. Individual proteins from all three families may include other, non-conserved domains that are not shown in the figures. (b) Crystal structures of Ski2-like (Mtr4)(28), DEAH/RHA (Prp43)(30) and DEAD-box (Mss116)(54) helicases. Domains are colored as in (a). The nucleotide (ADP for Mtr4 and Prp43, and ADPNP for Mss116) is shown in red and co-crystallized ssRNA bound to Mtr4 and Mss116 is shown in black. The β hairpin within D2 in Ski2-like and DEAH/RHA helicases that is thought to function as a pin during RNA unwinding is highlighted in pink.

Figure 2. Helicases that function in ribosome biogenesis

(a) S. cerevisiae helicases that function in biogenesis of the large and small ribosomal subunits. SSU: small subunit, LSU: large subunit. Essential helicases are shown in bold. DEAD-box, DEAH/RHA and Ski2-like helicases are shown in green, blue and orange, respectively. (b) Known and proposed roles of RNA helicases in ribosome biogenesis. SnoRNA-related roles include promoting binding and dissociation of snoRNAs, as well as rearrangements associated with snoRNA-guided cleavage events. Helicases indicated as promoting non-snoRNA-mediated rearrangements facilitate pre-rRNA cleavage at specific, snoRNA-independent processing sites (see text for details).

Figure 3. Helicase-mediated rearrangements in splicing

DEAD-box proteins are green, DEAH/RHA proteins are blue, and Ski2-like proteins are orange. Abbreviations in the figure are BP (branchpoint, shown as A in the cycle), Bbp (BP binding protein, aka Msl5), BSL (branchpoint stemloop), and SL (stemloop). For Prp2, Prp22, and Brr2, experimental evidence indicates interaction with a specific RNA strand and a direction of translocation (see text), which are shown by red arrows.