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Open AccessHighly AccessResearch article

Clustered microRNAs' coordination in regulating protein-protein interaction network

Xiongying Yuan* 1,2 email, Changning Liu* 1 email, Pengcheng Yang1,2 email, Shunmin He1,2 email, Qi Liao1,3 email, Shuli Kang1 email and Yi Zhao1 email

1Bioinformatics Group, Center for Advanced Computing Research, Institute of Computing Technology, Chinese Academy of Sciences, Beijing, PR China

2Graduate School of Chinese Academy of Sciences, Beijing, PR China

3Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, PR China

author email corresponding author email* Contributed equally

BMC Systems Biology 2009, 3:65doi:10.1186/1752-0509-3-65

Published: 26 June 2009

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.

Conclusion

In summary, this work supports the hypothesis of intra-cluster coordination and investigates the extent of this coordination.


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