Analysis of electric moments of RNA-binding proteins: implications for mechanism and prediction

Ahmad, Shandar; Sarai, Akinori
January 2011
BMC Structural Biology;2011, Vol. 11 Issue 1, p8
Academic Journal
Background: Protein-RNA interactions play important role in many biological processes such as gene regulation, replication, protein synthesis and virus assembly. Although many structures of various types of protein-RNA complexes have been determined, the mechanism of protein-RNA recognition remains elusive. We have earlier shown that the simplest electrostatic properties viz. charge, dipole and quadrupole moments, calculated from backbone atomic coordinates of proteins are biased relative to other proteins, and these quantities can be used to identify DNA-binding proteins. Closely related, RNA-binding proteins are investigated in this study. In particular, discrimination between various types of RNA-binding proteins, evolutionary conservation of these bulk electrostatic features and effect of conformational changes by complex formation are investigated. Basic binding mechanism of a putative RNA-binding protein (HI1333 from Haemophilus influenza) is suggested as a potential application of this study. Results: We found that similar to DNA-binding proteins (DBPs), RNA-binding proteins (RBPs) also show significantly higher values of electric moments. However, higher moments in RBPs are found to strongly depend on their functional class: proteins binding to ribosomal RNA (rRNA) constitute the only class with all three of the properties (charge, dipole and quadrupole moments) being higher than control proteins. Neural networks were trained using leave-one-out cross-validation to predict RBPs from control data as well as pair-wise classification capacity between proteins binding to various RNA types. RBPs and control proteins reached up to 78% accuracy measured by the area under the ROC curve. Proteins binding to rRNA are found to be best distinguished (AUC = 79%). Changes in dipole and quadrupole moments between unbound and bound structures were small and these properties are found to be robust under complex formation. Conclusions: Bulk electric moments of proteins considered here provide insights into target recognition by RNA-binding proteins, as well as ability to recognize one type of RBP from others. These results help in understanding the mechanism of protein-RNA recognition, and identifying RNA-binding proteins.


Related Articles

  • RNA-binding protein HuR mediates cytoprotection through stimulation of XIAP translation. Durie, D; Lewis, S M; Liwak, U; Kisilewicz, M; Gorospe, M; Holcik, M // Oncogene;3/24/2011, Vol. 30 Issue 12, p1460 

    Expression of the intrinsic cellular caspase inhibitor XIAP is regulated primarily at the level of protein synthesis. The 5' untranslated region harbours an Internal Ribosome Entry Site (IRES) motif that supports cap-independent translation of XIAP mRNA during conditions of cellular stress. In...

  • PLoS ONE: Study of ribosome evolution challenges 'RNA World' hypothesis.  // Biomedical Market Newsletter;3/21/2012, Vol. 21, p1 

    The article offers information on a new research finding which challenges the old RNA hypothesis and revealed the existence of protein-RNA interaction in protein synthesis before the evolution of ribosomes.

  • Molecular biology: Noncoding RNAs decapped.  // Nature;3/1/2012, Vol. 483 Issue 7387, p9 

    The article reports on the protective decapped of long noncoding ribonucleic acid (lncRNAs) in the gene regulation of the yeast.

  • Large-Scale Computational Modeling of Genetic Regulatory Networks. M. Stetter; G. Deco; M. Dejori // Artificial Intelligence Review;Oct2003, Vol. 20 Issue 1/2, p75 

    The perhaps most important signaling network in living cells is constituted by the interactions of proteins with the genome – the regulatory genetic network of the cell. From a system-level point of view, the various interactions and control loops, which form a genetic network, represent the...

  • The Prethalamus Is Established during Gastrulation and Influences Diencephalic Regionalization. Staudt, Nicole; Houart, Corinne // PLoS Biology;Apr2007, Vol. 5 Issue 4, p0878 

    The vertebrate neural plate contains distinct domains of gene expression, prefiguring the future brain areas. In this study, we draw an extended expression map of the rostral neural plate that reveals discrete domains inside the presumptive posterior forebrain. We show, by fate mapping, that...

  • RNA-binding proteins and translational regulation in axons and growth cones. Hörnberg, Hanna; Holt, Christine // Frontiers in Neuroscience;May2013, Vol. 7, p1 

    RNA localization and regulation play an important role in the developing and adult nervous system. In navigating axons, extrinsic cues can elicit rapid local protein synthesis that mediates directional or morphological responses. The mRNA repertoire in axons is large and dynamically changing,...

  • Structure of a bacterial 30S ribosomal subunit at 5.5 A resolution. Clemons Jr., William M.; May, Joanna L.C.; Wimberly, Brian T.; McCutcheon, John P.; Capel, Malcolm S.; Ramakrishnan, V. // Nature;8/26/1999, Vol. 400 Issue 6747, p833 

    Discusses the 30S ribosomal subunit, which binds messenger RNA and the anticodon stem-loop of transfer RNA during protein synthesis. Presentation of a crystallographic analysis of the structure of the subunit from the bacterium Thermus thermophilus; Visibility of the phosphate backbone of the...

  • SynGAP Regulates Protein Synthesis and Homeostatic Synaptic Plasticity in Developing Cortical Networks. Wang, Chih-Chieh; Held, Richard G.; Hall, Benjamin J. // PLoS ONE;Dec2013, Vol. 8 Issue 12, p1 

    Disrupting the balance between excitatory and inhibitory neurotransmission in the developing brain has been causally linked with intellectual disability (ID) and autism spectrum disorders (ASD). Excitatory synapse strength is regulated in the central nervous system by controlling the number of...

  • From Genes to Flower Patterns and Evolution: Dynamic Models of Gene Regulatory Networks. Chaos, �lvaro; Aldana, Max; Espinosa-Soto, Carlos; de Le�n, Berenice Garc�a Ponce; Arroyo, Adriana Garay; Alvarez-Buylla, Elena R. // Journal of Plant Growth Regulation;Dec2006, Vol. 25 Issue 4, p278 

    Genes and proteins form complex dynamical systems or gene regulatory networks (GRN) that can reach several steady states (attractors). These may be associated with distinct cell types. In plants, the ABC combinatorial model establishes the necessary gene combinations for floral organ cell...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics