4qpt

Publication Abstract from PubMed

The RNA recognition motif (RRM) is the far most abundant RNA binding domain. In addition to the typical beta1alpha1beta2beta3alpha2beta4 fold, various sub-structural elements have been described and reportedly contribute to the high functional versatility of RRMs. The heterogeneous nuclear ribonucleoprotein L (hnRNP L) is a highly abundant protein of 64kDa comprising four RRM domains. Involved in many aspects of RNA metabolism, hnRNP L specifically binds to RNAs containing CA repeats or CA-rich clusters. However, a comprehensive structural description of hnRNP L including its sub-structural elements is missing. Here, we present the structural characterization of the RRM domains of hnRNP L and demonstrate their function in repressing exon 4 of SLC2A2. By comparison of the sub-structural elements between the two highly similar paralog families of hnRNP L and PTB, we defined signatures underlying interacting C-terminal coils (ICCs), the RRM34 domain interaction and RRMs with a C-terminal fifth beta-strand, a variation we denoted vRRMs. Furthermore, computational analysis revealed new putative ICC-containing RRM families and allowed us to propose an evolutionary scenario explaining the origins of the ICC and fifth beta-strand sub-structural extensions. Our studies provide insights of domain requirements in alternative splicing mediated by hnRNP L and molecular descriptions for the sub-structural elements. In addition, the analysis presented may help to classify other abundant RRM extensions and to predict structure-function relationships.

The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein.,Blatter M, Dunin-Horkawicz S, Grishina I, Maris C, Thore S, Maier T, Bindereif A, Bujnicki JM, Allain FH J Mol Biol. 2015 Jun 5. pii: S0022-2836(15)00318-6. doi:, 10.1016/j.jmb.2015.05.020. PMID:26051023^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.