2mqn

From Proteopedia

Structural Investigation of hnRNP L

Structural highlights

2mqn is a 1 chain structure with sequence from Rattus norvegicus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HNRPL_RAT Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements. Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts. Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter. As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPK and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (By similarity).[UniProtKB:P14866]

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.

References

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