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Link to original content: https://doi.org/10.1038/nrm2178
RNA-binding proteins: modular design for efficient function | Nature Reviews Molecular Cell Biology
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RNA-binding proteins: modular design for efficient function

Nature Reviews Molecular Cell Biology volume 8, pages 479–490 (2007)Cite this article

Key Points

  • Many RNA-binding proteins have a modular structure and are composed of multiple repeats of a few small domains. By arranging the domains in various ways, these proteins can satisfy the diverse biological roles they play.

  • The modular nature of RNA-binding proteins allows them to satisfy their functional roles in various ways. Multiple domains allow the recognition of long sequence stretches, sequences that are separated from each other or even sequences on different RNAs. The domains can pre-organize themselves to arrange the RNA in a particular topology or, conversely, the proteins can be arranged to interact with a particular RNA structure. Last, enzymatic domains can be combined with RNA-binding domains to regulate catalytic activity.

  • One of the most common arrangements is to have two domains separated by a short linker. This allows the protein to create a larger interaction surface that can interact with many more nucleotides than the isolated domains.

  • Interdomain linkers often have key functional roles in organizing the domains to facilitate the recognition of a particular substrate.

  • Many of the RNA-binding modules can participate in protein–protein interactions, which can facilitate assembly of higher-order complexes.

  • RNA-binding modules can be combined with enzymatic domains to properly position the catalytic domain on the RNA or to regulate the activity of the enzyme.

Abstract

Many RNA-binding proteins have modular structures and are composed of multiple repeats of just a few basic domains that are arranged in various ways to satisfy their diverse functional requirements. Recent studies have investigated how different modules cooperate in regulating the RNA-binding specificity and the biological activity of these proteins. They have also investigated how multiple modules cooperate with enzymatic domains to regulate the catalytic activity of enzymes that act on RNA. These studies have shown how, for many RNA-binding proteins, multiple modules define the fundamental structural unit that is responsible for biological function.

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Figure 1: Many RNA-binding proteins have a modular structure.
Figure 2: RNA-binding modules are combined to perform multiple functional roles.
Figure 3: How RNA-binding modules recognize RNA.
Figure 4: Protein–protein interactions and protein-RNA interactions define the site of spliceosomal assembly.
Figure 5: RNA-binding modules function together to recognize a specific RNA.
Figure 6: Modular architecture allows for the regulation of the catalytic activity of enzymatic domains.

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Acknowledgements

Work in our laboratories is supported by grants from National Institutes of Health–National Institute of General Medical Sciences (G.V. and C.M.). We apologize to the many colleagues whose work could not be properly referenced owing to lack of space.

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Authors and Affiliations

  1. Department of Chemistry, University of Washington, Seattle, 98195, Washington, USA

    Gabriele Varani

  2. Department of Biochemistry, University of Washington, Seattle, 98195, Washington, USA

    Bradley M. Lunde & Gabriele Varani

  3. Department of Biomolecular Structure and Design, University of Washington, Seattle, 98195, Washington, USA

    Bradley M. Lunde

  4. Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, 02111, Massachusetts, USA

    Claire Moore

Authors
  1. Bradley M. Lunde
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Correspondence to Gabriele Varani.

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DATABASES

Protein Data Bank

1C9S

1EC6

1EKZ

1M8Y

1RGO

1SI3

1U04

1UN6

1URN

1YTU

2ASB

2ESE

2FFL

2IX1

2NN6

FURTHER INFORMATION

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Gabriele Varani's homepage

Glossary

Ribonucleoprotein

(RNP). A complex that contains proteins and RNA. The RNP motif refers to the two conserved sequence elements found in the RNA-recognition motif (RRM) (in its two central β-strands) that participate in RNA recognition and identify the RRM domain at the sequence level.

Orthologous proteins

Proteins that are direct evolutionary counterparts, that retain the same function in different organisms and that have arisen due to speciation events but not through the process of gene duplication (paralogous proteins).

Zinc finger

A class of DNA- and RNA-binding proteins characterized by a Cys- and His-rich domain that chelates a zinc ion. Different classes of zinc-finger proteins contain different combinations of metal-binding amino acids: CCHH zinc fingers contain two Cys and two His residues, whereas CCCH and CCHC zinc-binding motifs contain three Cys and a single His residue in different topological arrangements.

AU-rich element

Sequences rich in A and U nucleotides that are found in the 3′ untranslated regions of mRNAs that promote stability or degradation of their associated RNAs, thus providing a mechanism for the control of gene expression.

Argonaute proteins

A family of proteins that are characterized by the presence of two homology domains, PAZ and PIWI. The proteins provide the essential catalytic activity for diverse RNA-silencing pathways.

RNA-induced silencing complex

A multicomponent ribonucleoprotein complex that cleaves specific mRNAs that are targeted for degradation by homologous double-stranded RNAs during the process of RNA interference.

Pumilio (Puf) family of proteins

A highly conserved family of RNA-binding proteins with a C-terminal RNA-binding domain that is composed of eight tandem repeats, with each repeat recognizing a single nucleotide.

Exosome

A multisubunit 3′→5′ exonuclease that functions in the nucleus and the cytoplasm in several different RNA-processing and RNA-degradation pathways.

Exon-junction complex

A multisubunit protein complex that is deposited on the mRNA during the splicing reaction near the splice site. It remains bound to the RNA during subsequent gene-expression events, and serves as a platform to recruit nuclear and cytoplasmic factors that influence mRNA localization, transport, stability and translation.

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Lunde, B., Moore, C. & Varani, G. RNA-binding proteins: modular design for efficient function. Nat Rev Mol Cell Biol 8, 479–490 (2007). https://doi.org/10.1038/nrm2178

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