Prediction of a new class of RNA recognition motif |
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Authors: | Núria Cerdà-Costa Jaume Bonet M Rosario Fernández Francesc X Avilés Baldomero Oliva Sandra Villegas |
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Institution: | 1.Departament de Bioquímica i Biologia Molecular, Unitat de Biociències,Universitat Autònoma de Barcelona,Cerdanyola del Vallès,Spain;2.Structural Bioinformatics Group (GRIB), Barcelona Research Park of Biomedicine (PRBB),Universitat Pompeu Fabra,Barcelona,Spain;3.Institut de Biotecnologia i Biomedicina,Universitat Autònoma de Barcelona,Cerdanyola del Vallès,Spain |
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Abstract: | The observation that activation domains (AD) of procarboxypeptidases are rather long compared to the pro-regions of other
zymogens raises 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 compared the overall pro-domain tertiary structure with
several proteins belonging to the same fold in the structural classification of proteins (SCOP) database by using structure
and sequence comparisons. The best score obtained was between the activation domain of human procarboxypeptidase A4 (ADA4h)
and the human U1A protein from the U1 snRNP. Structural alignment 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 electrophoretic mobility shift assays 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 suggest the sharing of a common ancestor with other RNA recognition motifs. However, the
fact that key residues preventing activity within the proenzyme are also key residues for RNA binding might have induced the
activation domains of procarboxypeptidases to evolve from the canonical RNP1 and RNP2 sequences. |
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