RNA helicases and abiotic stress

Abstract

RNA helicases function as molecular motors that rearrange RNA secondary structure, potentially performing roles in any cellular process involving RNA metabolism. Although RNA helicase association with a range of cellular functions is well documented, their importance in response to abiotic stress is only beginning to emerge. This review summarizes the available data on the expression, biochemistry and physiological function(s) of RNA helicases regulated by abiotic stress. Examples originate primarily from non-mammalian organisms while instances from mammalian sources are restricted to post-translational regulation of helicase biochemical activity. Common emerging themes include the requirement of a cold-induced helicase in non-homeothermic organisms, association and regulation of helicase activity by stress-induced phosphorylation cascades, altered nuclear-cytoplasmic shuttling in eukaryotes, association with the transcriptional apparatus and the diversity of biochemical activities catalyzed by a subgroup of stress-induced helicases. The data are placed in the context of a mechanism for RNA helicase involvement in cellular response to abiotic stress. It is proposed that stress-regulated helicases can catalyze a nonlinear, reversible sequence of RNA secondary structure rearrangements which function in RNA maturation or RNA proofreading, providing a mechanism by which helicase activity alters the activation state of target RNAs through regulation of the reaction equilibrium.

Figure 1

Helicase activation of RNA substrates. The traditional proposed function of RNA helicases involves unwinding of dsRNA in a linear unidirectional reaction. The discovery of helicases with additional biochemical activities, including the ‘clearing’ of proteins and annealing of complementary RNAs indicates the potential for expanded roles in RNA metabolic pathways. Three different roles are shown here. A linear sequence of RNA maturation steps, each of which is catalyzed by a unique helicase which can concomitantly rearrange RNA secondary structure and clear proteins from the RNA. Successive rounds of helicase RNP remodeling combined with RBP action will generate a linear series of steps catalyzing RNA maturation, thereby activating the RNA substrate. The discovery of RNA helicases that can anneal complementary RNAs (DED1, p68, p72 and CrhR) provides the ability to reverse a helicase driven activation-unwinding reaction, thereby maintaining the substrate RNA in an inactive or immature state. Finally, the ability to both unwind and anneal RNA substrates provides the potential for RNA proofreading, enabling improperly folded RNAs to be reactivated. The reversibility of each of these reactions also provides the potential to regulate the equilibrium of the reaction. RNA helicase phosphorylation in response to stress activated signal transduction pathways is another mechanism by which RNA helicase activity can be regulated. RBP, RNA-binding protein.

Figure 2

Roles for abiotic stress-induced RNA helicases. Stabilized, non-functional RNAs are recognized and unwound by the abiotic stress (low temperature in this example)-induced RNA helicase. Cold-induced RBPs belonging to the Rbp or Csp families in cyanobacteria (71) and E.coli or Bacillus (72), respectively, potentially bind to the RNA helicase-generated ssRNA, thereby inhibiting spontaneous reversion to dsRNA, and permit translation initiation to proceed. Similar scenarios can be envisioned for helicases involved in prokaryotic and eukaryotic RNA degradation pathways. It is also possible for this model to function on constitutively expressed RNAs that are not translated in the absence of a stress-induced helicase. Stress-induced production of an RNA helicase which interacts with a specific secondary structure in these stored RNAs can then initiate their translation, thereby allowing post-transcriptional regulation of an entire response system through regulated expression of a single RNA helicase gene.