InterPro domain: IPR000504

Many eukaryotic proteins containing one or more copies of a putative RNA-binding domain of about 90 amino acids are known to bind single-stranded RNAs [ 1 , 2 , 3 ]. The largest group of single strand RNA-binding proteins is the eukaryotic RNA recognition motif (RRM) family that contains an eight amino acid RNP-1 consensus sequence [ 4 , 5 ]. RRM proteins have a variety of RNA binding preferences and functions, and include heterogeneous nuclear ribonucleoproteins (hnRNPs), proteins implicated in regulation of alternative splicing (SR, U2AF, Sxl), protein components of small nuclear ribonucleoproteins (U1 and U2 snRNPs), and proteins that regulate RNA stability and translation (PABP, La, Hu) [ 6 , 6 , 6 ]. The RRM in heterodimeric splicing factor U2 snRNP auxiliary factor (U2AF) appears to have two RRM-like domains with specialised features for protein recognition [ 6 ]. The motif also appears in a few single stranded DNA binding proteins.

The typical RRM consists of four anti-parallel beta-strands and two alpha-helices arranged in a beta-alpha-beta-beta-alpha-beta fold with side chains that stack with RNA bases. Specificity of RNA binding is determined by multiple contacts with surrounding amino acids. A third helix is present during RNA binding in some cases [ 7 ]. The RRM is reviewed in a number of publications [ 8 , 9 , 10 ].

1. Heterogeneous nuclear ribonucleoprotein particles and the pathway of mRNA formation. Trends Biochem. Sci. 13, 86-91
2. Genomic structure and amino acid sequence domains of the human La autoantigen. J. Biol. Chem. 263, 18043-51
3. A single domain of yeast poly(A)-binding protein is necessary and sufficient for RNA binding and cell viability. Mol. Cell. Biol. 7, 3268-76
4. RNA-binding proteins as developmental regulators. Genes Dev. 3, 431-7
5. A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein. Cell 57, 89-101
6. U2AF homology motifs: protein recognition in the RRM world. Genes Dev. 18, 1513-26
7. Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res. 21, 5803-16
8. RNA recognition: towards identifying determinants of specificity. Trends Biochem. Sci. 16, 214-20
9. The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression. FEBS J. 272, 2118-31
10. Structural basis for recognition and sequestration of UUU(OH) 3' temini of nascent RNA polymerase III transcripts by La, a rheumatic disease autoantigen. Mol. Cell 21, 75-85