title: Clustered microRNAs' coordination in regulating protein-protein interaction network.
abstract: BACKGROUND
  MicroRNAs (miRNAs), a growing class of small RNAs with crucial regulatory roles at the post-transcriptional level, are usually found to be clustered on chromosomes. However, with the exception of a few individual cases, so far little is known about the functional consequence of this conserved clustering of miRNA loci. In animal genomes such clusters often contain non-homologous miRNA genes. One hypothesis to explain this heterogeneity suggests that clustered miRNAs are functionally related by virtue of co-targeting downstream pathways.
  
  
  RESULTS
  Integrating of miRNA cluster information with protein protein interaction (PPI) network data, our research supports the hypothesis of the functional coordination of clustered miRNAs and links it to the topological features of miRNAs' targets in PPI network. Specifically, our results demonstrate that clustered miRNAs jointly regulate proteins in close proximity of the PPI network. The possibility that two proteins yield to this coordinated regulation is negatively correlated with their distance in PPI network. Guided by the knowledge of this preference, we found several network communities enriched with target genes of miRNA clusters. In addition, our results demonstrate that the variance of this propensity can also partly be explained by protein's connectivity and miRNA's conservation.
  
  
  CONCLUSIONS
  In summary, this work supports the hypothesis of intra-cluster coordination and investigates the extent of this coordination.
authors: Bioinformatics Group, Center for Advanced Computing Research, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, PR China. pkuying@126.com
authors: Xiongying
authors: X
authors: Yuan
authors: Changning
authors: C
authors: Liu
authors: Pengcheng
authors: P
authors: Yang
authors: Shunmin
authors: S
authors: He
authors: Qi
authors: Q
authors: Liao
authors: Shuli
authors: S
authors: Kang
authors: Yi
authors: Y
authors: Zhao
mesh_terms: D000818:Animals; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011506:Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D035683:MicroRNAs; D011506:Proteins