We studied the global correlation between protein complex association number and the number of miRNA target-site types at the 3′ UTRs of the gene encoding the protein. Interestingly, we have noticed a significant negative correlation between them (ρnumber of miRNA hits vs. protein complex association number = -0.102, P = 2.0×10-2, N = 513 [TargetScan]; ρnumber of miRNA hits vs. protein complex number = -0.191, P = 3.8×10-2, N = 118 [miRWalk]) (Supplementary Fig. 1A) which suggests that the proteins with low complex association number could be more targeted by miRNA compared to the proteins with high complex association number. Although the reported effect of miRNA on protein complex is significant, but of a very small magnitude which implies that protein complex association number is not tightly regulated by miRNA target. It was evident that highly sensitive nature of multi-protein complex towards their expression variation  may restrain the protein complex to be regulated by miRNA. Likewise, proteins that are shared across different complexes require a highly orchestrate expression pattern, frequent targeting by miRNA may perturb their expression coordination which also can damage their functional activity. Thus proteins, present in a large number of protein complexes turn down the robust regulation of miRNA.
Previous findings that proteins attached with multiple protein complexes tend to evolve slowly than those with fewer or no complex assembly . In our study, negative correlation between protein complex association number and miRNA regulation thus need clarification because genes with a higher level of miRNA regulation were reported to evolve more slowly . To unravel t...
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