Proteins binding to duplexed RNA: one motif, multiple functions

doi:10.1016/S0968-0004(00)01580-2

Trends in Biochemical Sciences

Volume 25, Issue 5, 1 May 2000, Pages 241-246

https://doi.org/10.1016/S0968-0004(00)01580-2 Get rights and content

Abstract

Highly structured and double-stranded (ds) RNAs are adaptable and potent biochemical entities. They interact with dsRNA-binding proteins (RBPs), the great majority of which contain a sequence called the dsRNA-binding motif (dsRBM). This ∼70-amino-acid sequence motif forms a tertiary structure that interacts with dsRNA, with partially duplexed RNA and, in some cases, with RNA–DNA hybrids, generally without obvious RNA sequence specificity. At least nine families of functionally diverse proteins contain one or more dsRBMs. The motif also participates in complex formation through protein–protein interactions.

Section snippets

RNA binding to the dsRBM

RNA–protein interactions are manifested in the 1.9 Å resolution crystal structure⁷ of dsRBM2 from the Xenopus laevis protein Xlrbpa complexed with dsRNA, shown in Fig. 2a. Two dsRNAs, each 10 bp long, are stacked end-wise to approximate a continuous helix, 16 base pairs of which are covered by the dsRBM. The RNA is predominantly A-form, and contacts with the motif take place on one face of the duplex, spanning two minor grooves and the major groove between them. Three structural elements of the

Nine protein families (at least)

The dsRBM is found in proteins (and protein sequence fragments) from diverse sources, including viruses, bacteria, and lower and higher eukaryotes. Considering sequence homology, both within the motifs and outside them, as well as the number and distribution of their dsRBMs, most of the proteins fall into one of nine major groups (see Fig. 1 and Table 1). Prototypical representatives of these nine dsRBP families are drawn schematically in Fig. 3, which diagrams the patterns of dsRBMs and

Functions of dsRNA-binding proteins

The nine families of dsRBPs in Fig. 3 can be divided into two groups: enzymes with well-established activities and RBPs to which no enzymatic function has (yet) been attributed. The enzyme group includes RHA, RNase III, ADAR1 and ADAR2, all of which modify RNA structure (via unwinding, cleavage and deamination), and PKR, for which dsRNA is an effector. The second group includes Staufen and E3L, whose functions entail RNA binding, and two protein families (NF90 and TRBP) for which the

Conclusions and conundrums

The dsRBM is a widespread structural module subserving a variety of functional roles in at least nine families of highly conserved proteins. It could be responsible for specific RNA recognition (as in Staufen) or essential for catalytic activity (as in ADAR); it can regulate the functional status of the dsRBP that contains it (as in PKR) or of another dsRBP (as in E3L); and its presence in proteins whose functions remain to be defined suggests that it also plays other roles. A remarkable

Acknowledgements

Our work is supported by grant number AI34552 from the National Institute of Allergy and Infectious Disease, NIH. We thank Tsafi Pe’ery for suggestions and apologize to readers and authors alike for the omission of many references owing to space constraints.

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^*: Present address: Dept of Biochemistry, University of Cambridge, Cambridge, UK CB2 1QW.

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Trends in Biochemical Sciences

ReviewProteins binding to duplexed RNA: one motif, multiple functions

Abstract

Section snippets

RNA binding to the dsRBM

Nine protein families (at least)

Functions of dsRNA-binding proteins

Conclusions and conundrums

Acknowledgements

Virology

Prog. Nucleic Acids Res. Mol. Biol.

J. Mol. Biol.

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Mol. Biol.

J. Biol. Chem.

J. Biol. Chem.

Cell

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Cell

Cell

A conserved double-stranded RNA-binding domain

Proc. Natl. Acad. Sci. U. S. A.

Two RNA-binding motifs in the double-stranded RNA activated protein kinase, DAI

Genes Dev.

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EMBO J.

NMR solution structure of a dsRNA binding domain from Drosophila Staufen protein reveals homology to the N-terminal domain of ribosomal protein S5

EMBO J.

Structure of the double-stranded RNA-binding domain of the protein kinase PKR reveals the molecular basis of its dsRNA-mediated activation

EMBO J.

Molecular basis of double-stranded RNA-protein interactions: structure of a dsRNA-binding domain complexed with dsRNA

EMBO J.

Binding of the protein kinase PKR to RNAs with secondary structure defects: role of the tandem A-G mismatch and noncontiguous helixes

Biochemistry

Expanded CUG repeat RNAs form hairpins that activate the double-stranded-RNA-dependent protein kinase PKR

RNA

Two functionally distinct RNA binding motifs in the regulatory domain of the protein kinase DAI

Mol. Cell. Biol.

The NTPase/helicase activities of Drosophila maleless, an essential factor in dosage compensation

EMBO J.

Review
Proteins binding to duplexed RNA: one motif, multiple functions