DEAD-Box RNA Helicases

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 targets^2,3. 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 DDX3 in FFPE seminoma by IHC.

Detection of human DDX27 in FFPE ovarian carcinoma by IHC.

Detection of human DDX20 in FFPE breast carcinoma by IHC.

References

1. Linder P, Jankowsky E. 2011. From unwinding to clamping – the DEAD box RNA helicase family. Nat Rev Mol Cell Biol. Jul 22;12(8):505-516.

2. Rocak S, Linder P. 2004. Dead-box proteins: the driving forces behind RNA metabolism. Nat Rev Mol Cell Biol. Mar 5(3):232-241.

3. Russell R, Jarmoskaite I, Lambowitz A. 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590237/Toward a molecular understanding of RNA remodeling by DEAD-box proteins. RNA Biol. Jan 1;10(1):44-55.

4. Mallam AL, Del Campo M, Gilman B, Sidote DJ, Lambowitz AM. 2012. Structural basis for RNA duplex recognition and unwinding by the DEAD-box helicase Mss116p. Nature. 490(7418):121-125.

5. Abdelhaleem M. 2004. Do human RNA helicases have a role in cancer? Biochimica et Biophysica Acta. Jul 6;1704(1):37–46.

6. Schröder M. 2011. Viruses and the human DEAD box helicase DDX3: inhibition or exploitation? Biochem Soc Trans. Apr,39(2):679–683.

DEAD-Box RNA Helicases

Bethyl's current portfolio of DEAD-Box RNA helicases antibodies:

References