Prediction of a new class of RNA recognition motif

Abstract

The observation that activation domains (AD) of procarboxypeptidases are rather long, compared to pro-regions of other zymogens, points out the possibility that they could play additional roles apart from precluding enzymatic activity within the proenzyme and helping in its folding process. In the present work, we have compared the overall pro-domain tertiary structure with several proteins belonging to the same fold in SCOP by using structure and sequence comparisons. The best score has been obtained between the activation domain of the human procarboxypeptidase A4 (ADA4h) and the human U1A protein from the U1 snRNP.Structural alignment has revealed the existence of RNP1-and RNP2-related sequences in ADA4h. After modeling ADA4h on U1A, the new structure was used to extract a new sequence pattern characteristic for important residues at key positions. The new sequence pattern allowed scanning protein sequences to predict the RNA-binding function for 32 sequences undetected by PFAM. Unspecific RNA EMSA experimentally supported the prediction that ADA4h binds an RNA motif similar to the U1A binding-motif of stem-loop II of U1 small nuclear RNA. The experiments carried out with ADA4h in the present work Manuscript Click here to download Manuscript: JMMO1391R2_final.doc 2 suggest the sharing of a common ancestor with other RRMs. However, the fact that key residues preventing activity within the proenzyme are also key residues for RNA binding might induce the activation domains of procarboxypeptidases to evolve from the canonical RNP1 and 2 sequences.

Mutagenesis of ARS2 Domains To Assess Possible Roles in Cell Cycle Progression and MicroRNA and Replication-Dependent Histone mRNA Biogenesis

“…During our bioinformatics analysis, we identified a previously undescribed RRM domain within metazoan ARS2. Canonical RRM domains have two conserved sequence motifs: (31). Critical aromatic residues (in bold) of RNP1 and RNP2 form stacked pi interactions with RNA bases, and the arginine or lysine of RNP1 forms multiple hydrogen bonds with nitrogenous bases (32).…”