Tài liệu Báo cáo khoa học: The RNA recognition motif, a plastic RNA-binding platform to regulate

MINIREVIEW

The RNA recognition motif, a plastic RNA-binding platform

to regulate post-transcriptional gene expression

Christophe Maris*, Cyril Dominguez* and Fre´de´ric H.-T. Allain

Institute for Molecular Biology and Biophysics, Swiss Federal Institute of Technology Zurich, ETH-Ho¨nggerberg, Zu¨rich, Switzerland

History – what defines an RRM?

The RNA recognition motif (RRM), also known as

the RNA-binding domain (RBD) or ribonucleopro￾tein domain (RNP), was first identified in the late

1980s when it was demonstrated that mRNA precur￾sors (pre-mRNA) and heterogeneous nuclear RNAs

(hnRNAs) are always found in complex with proteins

(reviewed in [1]). Biochemical characterizations of the

mRNA polyadenylate binding protein (PABP) and

the hnRNP protein C shed light on a consensus

RNA-binding domain of approximately 90 amino

acids containing a central sequence of eight con￾served residues that are mainly aromatic and posi￾tively charged [2,3]. This sequence, termed the RNP

consensus sequence, was thought to be involved in

RNA interaction and was defined as Lys⁄Arg￾Gly-Phe ⁄Tyr-Gly ⁄Ala-Phe ⁄Tyr-Val ⁄Ile ⁄Leu-X-Phe ⁄Tyr,

where X can be any amino acid. Later, a second

consensus sequence less conserved than the previously

characterized one [1] was identified. This six residue

sequence located at the N-terminus of the domain

Keywords

RNA recognition motif; protein–RNA

complex; structure–function relationship;

RNA-binding specificity

Correspondence

F. H.-T. Allain, Institute for Molecular

Biology and Biophysics, Swiss Federal

Institute of Technology Zurich, ETH￾Ho¨nggerberg, CH-8093 Zu¨rich, Switzerland

Fax: +41 1 6331294

Tel: +41 1 6333940

E-mail: [email protected]

Website: http://www.mol.biol.ethz.ch/

groups/allain_group

*These authors contributed equally to the

work

(Received 16 December 2004, accepted

7 March 2005)

doi:10.1111/j.1742-4658.2005.04653.x

The RNA recognition motif (RRM), also known as RNA-binding domain

(RBD) or ribonucleoprotein domain (RNP) is one of the most abundant

protein domains in eukaryotes. Based on the comparison of more than 40

structures including 15 complexes (RRM–RNA or RRM–protein), we

reviewed the structure–function relationships of this domain. We identified

and classified the different structural elements of the RRM that are import￾ant for binding a multitude of RNA sequences and proteins. Common

structural aspects were extracted that allowed us to define a structural leit￾motif of the RRM–nucleic acid interface with its variations. Outside of the

two conserved RNP motifs that lie in the center of the RRM b-sheet, the

two external b-strands, the loops, the C- and N-termini, or even a second

RRM domain allow high RNA-binding affinity and specific recognition.

Protein–RRM interactions that have been found in several structures rein￾force the notion of an extreme structural versatility of this domain support￾ing the numerous biological functions of the RRM-containing proteins.

Abbreviations

ACF, APOBEC-1 complementary factor; CBP, cap binding protein; CstF, cleavage stimulation factor; hnRNP, heterogeneous nuclear

ribonucleoprotein; HuD, Hu protein D; LRR, leucine rich repeat; MIF4G, middle domain of the translation initiation factor 4 G; PABP,

polyadenylate binding protein; PIE, polyadenylation inhibition element; PTB, polypyrimidine tract binding protein; RBD, RNA-binding domain;

RNP, ribonucleoprotein; RRM, RNA recognition motif; SR, serine/arginine rich proteins; TLS, translocated in liposarcoma; U1A, U2A¢, U2B¢:

U1 snRNP proteins A, A¢, B¢; U2AF, U2 snRNP auxiliary factor; UHM, U2AF homology motif; UPF, up-frameshift protein.

2118 FEBS Journal 272 (2005) 2118–2131 ª 2005 FEBS