The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein
The Signature of the Five-Stranded vRRM Fold Defined by Functional, Structural and Computational Analysis of the hnRNP L Protein
复制标题
DOI：
10.1016/j.jmb.2015.05.020
复制
发表时间：
2015-09-25
影响因子：
5.6
通讯作者：
Allain, Frederic H. -T.
中科院分区：
文献类型：
--
作者：
Blatter, Markus;Dunin-Horkawicz, Stanislaw;Allain, Frederic H. -T.
The RNA recognition motif (RRM) is the far most abundant RNA binding domain. In addition to the typical beta(1)alpha 1 beta(2)beta(3)alpha(2)beta(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 (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. (C) 2015 Elsevier Ltd. All rights reserved.
