Contributed by Allison A. Curley, Ph.D.
RNA helicases, enzymes that use ATP to unwind double-stranded RNA, are critical mediators of virtually every element of RNA metabolism. The largest family of RNA helicases is the DEAD-box proteins, comprised of 37 members in humans1. First described in the late 1980s, DEAD-box proteins are now known to play diverse roles in a variety of cellular processes, including transcription, pre-mRNA splicing, ribosome biogenesis, nuclear export of RNA, translation, and RNA degradation – most often by inducing conformational changes of their RNA targets2,3. Some DEAD-box proteins target specific RNAs, while others act more generally3.
Despite their functional diversity, all members of the family contain a helicase core element that contains at least 12 conserved motifs across two domains (D1 and D2)1,3. DEAD-box proteins derive their name from the amino acid sequence of motif II (Asp-Glu-Ala-Asp or D-E-A-D) and are often abbreviated DDX (although many have one or more alternate names).
New research has shed light on the mechanism that governs the helicase activity of DEAD-box proteins. According to a recent model4, D1 binds ATP while D2 attaches to the target RNA. The two domains then undergo a conformational change, joining together to form an ATPase active site. By bending one of the RNA strands bound to D2, D1 then promotes the unwinding of the RNA-duplex.
Given their crucial role in normal cellular functioning, it is not surprising that DEAD-box proteins also implicated in disease. For example, the dysregulation of many family members that influence transcription, splicing, and translation (including DDX1, DDX2, DDX5, DDX6, and DDX53) has been linked to a wide variety of cancers5. In addition, DDX3 is required for the replication of both human immunodeficiency virus (HIV) and hepatitis C virus (HCV), and is a potential target for the development of interventions to combat these infections6.
Detection of human DDX20 in FFPE breast carcinoma by IHC. Antibody: Rabbit anti-DDX20 (A300-650A). Substrate: DAB.
Bethyl’s current portfolio of DEAD-Box RNA helicases antibodies: