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DEAD-box proteins: the driving forces behind RNA metabolism

Nature Reviews Molecular Cell Biology volume 5, pages 232–241 (2004)Cite this article

Key Points

  • RNA helicases of the DEAD-box protein family all have nine characteristic motifs. These motifs clearly distinguish this family from other, highly related, RNA helicase families such as the DEAH-box or the Ski2 families.

  • The motifs are contained within a core domain that is flanked by less-conserved regions, which are likely to represent specificity elements for substrate targeting, interaction with other proteins or cellular localization.

  • RNA helicases of the DEAD-box family are required for different cellular processes such as transcription, pre-mRNA processing, ribosome biogenesis, nuclear mRNA export, translation initiation, RNA turnover and organelle function.

  • The structure of the core element, which contains all the conserved motifs that are required for helicase activity, is very similar to viral RNA helicases and to DNA helicases, which indicates that the fundamental activities of these enzymes are similar.

  • ATP-binding and hydrolysis by the core element induce conformational changes that are responsible for the enzymatic activity of these proteins; that is, unwinding of duplex RNA or disrupting RNA–protein complexes.

  • The enzymatic activity varies among different proteins and can be more or less processive, parameters that are probably influenced by interacting partners and the substrate.

Abstract

RNA helicases from the DEAD-box family are found in almost all organisms and have important roles in RNA metabolism. They are associated with many processes ranging from RNA synthesis to RNA degradation. DEAD-box proteins use the energy from ATP hydrolysis to rearrange inter- or intra-molecular RNA structures or dissociate RNA–protein complexes. Such dynamic rearrangements are fundamental for many, if not all, steps in the life of an RNA molecule. Recent biochemical, genetic and structural data shed light on how these proteins power the metabolism of RNA within a cell.

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Figure 1: Structure of the Methanococcus jannaschii DEAD-box protein.
Figure 2: Cellular processes that require DEAD-box RNA helicases.
Figure 3: Possible modes of unwinding by DEAD-box RNA helicases.
Figure 4: Phylogram of DEAD-box proteins from the three kingdoms of life.

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Acknowledgements

We are grateful to members of the laboratory and the helicase community for continuous discussion. We acknowledge highly stimulating discussions and pertinent comments about this manuscript from M. Altmann, D. Belin, O. Cordin, F. Fuller-Pace, T. Lacombe, G. Owttrim, N.K. Tanner and the three referees. Work in our laboratory is supported by the Swiss National Science Foundation and the state of Geneva.

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Authors and Affiliations

  1. Departement de Biochimie Médicale, Centre Médical Universitaire, 1 rue Michel Servet, Genè, CH-1211 4, Switzerland

    Sanda Rocak & Patrick Linder

Authors
  1. Sanda Rocak
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  2. Patrick Linder
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Corresponding author

Correspondence to Patrick Linder.

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The authors declare no competing financial interests.

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DATABASES

Entrez

Cyt-19

DbpA

mHel61

Rhlb

SrmB

YxiN

Flybase

Vasa

The Protein Data Bank

1HV8

Saccharomyces genome database

Brr2

Dbp5

Ded1

Dhh1

Dob1

eIF4A

Mrh4

Mss116

Mud2

Prp5

Prp16

Prp22

Prp28

Prp43

Ski2

Sub2

Swiss-Prot

DP103

FURTHER INFORMATION

RNA helicases

Swiss-PDBviewer

BLAST searches for putative helicases

Glossary

HELICASE

An enzyme that unwinds double-stranded nucleic acids in an energy-dependent manner.

SKI2 FAMILY

RNA helicases that are related to DEAD-box proteins and named after Ski2, a yeast protein that is involved in RNA turnover.

WALKER A AND B MOTIFS

Amino-acid consensus sequences that are present in nucleotide-triphosphate (NTP)-binding proteins named after J. E. Walker who first described these motifs.

ARGININE FINGER

A catalytic residue that was first defined for Ras-GTPase-activating proteins (RasGAPs), and that supplies a catalytic arginine residue into the active site of Ras to increase the reaction rate.

SMALL NUCLEAR RNA (snRNA)

A small RNA molecule that functions in the nucleus by guiding the assembly of macromolecular complexes on the target RNA to allow site-specific modifications or processing reactions to occur.

RNPase

An enzyme that causes the dissociation of a ribonucleoprotein (RNP) complex by disrupting protein–RNA interactions.

PSEUDO-URIDYLATION

The conversion of a uridine residue within an RNA chain into a pseudouridine residue, which requires the scission and reattachment of the base to the sugar.

SMALL NUCLEOLAR RNA (snoRNA)

A small RNA molecule that functions in ribosome biogenesis in the nucleolus by guiding the assembly of macromolecular complexes on the target RNA to allow site-specific modifications or processing reactions to occur.

GROUP I INTRONS

A class of self-splicing introns, the excision of which in vivo is assisted by trans-acting protein factors.

KINETICALLY TRAPPED

A particular substrate conformation that cannot be used further without it being refolded with external assistence.

GUIDE RNA (gRNA)

A small RNA molecule that is complementary to a sequence that is to be modified or processed, and that guides proteins to this target.

RNase E

An exonucleolytic RNase that digests RNA in the 3′→5′ direction

POLYNUCLEOTIDE-PHOSPHORYLASE

(PNPase). An enzyme that hydrolyzes single-stranded polyribonucleotides processively in the 3′→5′ direction.

DEGRADOSOME

A complex of RNase E and polynucleotidephosphorylase (PNPase) that degrades RNA. The degradosome is assisted by a DEAD-box RNA helicase to allow degradation of structured RNAs

EXOSOME

A complex of several exonucleases that, assisted by RNA helicases, degrades RNAs in the nucleus and the cytoplasm.

SURVIVAL OF MOTOR NEURONS (SMN) PROTEIN

Product of the spinal muscular atrophy (SMA) disease gene. SMN is present in a large complex that functions in snRNP assembly, pre-mRNA splicing and transcription.

MICHAELIS CONSTANT

(Km). The Michaelis constant is equal to the substrate concentration at which the reaction rate is half its maximal value. A high Km indicates a weak binding, and a low Km indicates strong binding.

SERYL tRNA SYNTHETASE

An enzyme that catalyses the attachment of serine to the 3′ end of tRNAs containing the anticodons that correspond to serine. They belong to the family of aminoacyl-tRNA synthetases.

TURNOVER NUMBERS

(kcat). The number of substrate molecules that are converted into product by an enzyme molecule in a unit of time when the enzyme is fully saturated with substrate.

ΔG

The difference in free energy of a system at constant pressure and temperature. The more negative the ΔG, the more stable the duplex.

MICROSPORIDIA

Obligate intracellular parasites that have a reduced genome content.

NUCLEOMORPH

A vestigial nucleus-like structure that harbours the smallest eukaryotic genomes of an algal endosymbiont.

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Rocak, S., Linder, P. DEAD-box proteins: the driving forces behind RNA metabolism. Nat Rev Mol Cell Biol 5, 232–241 (2004). https://doi.org/10.1038/nrm1335

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