Blatter, Markus, Dunin-Horkawicz, Stanislaw, Grishina, Inna , Maris, Christophe , Thore, Stephane , Maier, Timm , Bindereif, Albrecht and Allain, Frédéric H.-T. (2015) The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein. Journal of Molecular Biology.

Abstract

The RNA recognition motif (RRM) is the far most abundant RNA binding domain. In addition to the typical 112324 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 64 kDa 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 (ICC), the RRM34 domain interaction and RRMs with a C-terminal 5th -strand, a variation we denoted vRRMs. Furthermore, computational analysis revealed new putative ICC-containing RRM families and allowed to propose an evolutionary scenario explaining the origins of the ICC and 5th -strand sub-structural extensions. Our studies provide insights of domain requirements in hnRNP L mediated alternative splicing 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.

Item Type:	Article
Keywords:	RNA Recognition Motif, repressor function, interacting C-terminal coil, fifth β-strand, evolutionary analysis
Date Deposited:	05 Mar 2016 00:45
Last Modified:	05 Mar 2016 00:45
URI:	https://oak.novartis.com/id/eprint/28579