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Structural mechanisms of RNA recognition: sequence-specific and non-specific RNA-binding proteins and the Cas9-RNA-DNA complex

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Abstract

RNA-binding proteins play crucial roles in RNA processing and function as regulators of gene expression. Recent studies have defined the structural basis for RNA recognition by diverse RNA-binding motifs. While many RNA-binding proteins recognize RNA sequence non-specifically by associating with 5′ or 3′ RNA ends, sequence-specific recognition by RNA-binding proteins is typically achieved by combining multiple modular domains to form complex binding surfaces. In this review, we present examples of structures from different classes of RNA-binding proteins, identify the mechanisms utilized by them to target specific RNAs, and describe structural principles of how protein–protein interactions affect RNA recognition specificity. We also highlight the structural mechanism of sequence-dependent and -independent interactions in the Cas9-RNA-DNA complex.

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Abbreviations

PPR:

Pentatricopeptide repeat

Pre-mRNA:

Precursor messenger RNA

RBDs:

RNA-binding domains

TPR:

Tetratricopeptide repeat

PUF:

Pumilio-FBF

TZF:

TTP-like zinc finger

AGO:

Argonaute-like

FBF:

fem-3 binding factor

ssRNA:

Single-stranded RNA

TTP:

Tristetraprolin

PIWI:

P-element-induced wimpy testes

PAZ:

PIWI, Argonaute, and Zwille

MDA5:

Melanoma differentiation-associated gene 5

RIG-I:

Retinoic acid-inducible gene I

PPP-RNA:

5′ triphosphate RNA

RRM:

RNA recognition motif

U2AF:

U2 auxiliary factor

hnRNP:

Heterogeneous nuclear ribonucleoprotein

CRISPR:

Clustered regularly interspaced short palindromic repeats

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Author notes

  1. Ting Ban

    Present address: Roche Innovation Center Shanghai, 720 Cailun Road, Shanghai, 201203, People’s Republic of China

Authors and Affiliations

  1. VARI-SIMM Center, Center for Structure and Function of Drug Targets, Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Ting Ban & H. Eric Xu

  2. Shanghai Center for Plant Stress Biology and Shanghai Institute of Plant Physiology and Ecology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, 300 Fenglin Road, Shanghai, 200032, China

    Ting Ban & Jian-Kang Zhu

  3. Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN, 47906, USA

    Jian-Kang Zhu

  4. Laboratory of Structural Sciences and Laboratory of Structural Biology and Biochemistry, Van Andel Research Institute, 333 Bostwick Ave., N.E, Grand Rapids, MI, 49503, USA

    Karsten Melcher & H. Eric Xu

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  1. Ting Ban
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  4. H. Eric Xu
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Correspondence to Ting Ban.

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Ban, T., Zhu, JK., Melcher, K. et al. Structural mechanisms of RNA recognition: sequence-specific and non-specific RNA-binding proteins and the Cas9-RNA-DNA complex. Cell. Mol. Life Sci. 72, 1045–1058 (2015). https://doi.org/10.1007/s00018-014-1779-9

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