MicroRNA regulation in Arabidopsis thaliana Diane Guo CUHK 6th IncoB, Aug.29, 2007

Outline Background Characterization of miRNA targets Interactions between miRNAs and various cellular pathways Coordinated regulation by miRNAs and transcription factors Summary

microRNA miRNAs are small endogenous RNA molecules (~22nt) found in plant and animals Regulate gene expression through targeted mRNA cleavage or translational repression Play critical roles in a variety of cellular processes such as development, cell proliferation, apoptosis, and stress response, etc

MiRNA processing and activity (borrowed from Ambion)

Mode of miRNA action in plants and animals (borrowed from Ambion)

Table 1 GO terms of miRNA targets (molecular function) GO ID GO Term Target P-value GO:0003700 GO:0004386 GO:0003677 GO:0008234 GO:0004842 GO:0051082 GO:0005524 GO:0016301 GO:0005554 transcription factor activity other enzyme activity DNA or RNA binding hydrolase activity protein binding nucleotide binding kinase activity molecular function unknown 139 9 89 14 17 10 44 58 333 0.0002 0.0006 0.0013 0.0026 0.0032 0.0076 0.01 1

Table 2 Feature of miRNA target Target Type Target Number High-link (>5) 78 Low-link (<=4) 45 Total 123

Table 2 Feature of miRNA target Role of target Positive regulation Negative regulation Total Regulating 27 28 55 Being regulated 21 14 35 48 42 90

MiRNAs more frequently target genes with less transcription factor binding site

Summary We systematically analyzed the characteristics of miRNA targets. MiRNAs with multi-gene families are more likely to target TFs, and miRNAs represented by single gene tend to target non-TFs. To systematically investigate the interactions between miRNAs and various cellular pathways, we analyzed the miRNA targets distribution in the pathways and found that miRNAs regulate the pathway through selectively interacting with positive regulatory modules and highly connected nodes. We found that miRNA preferentially target genes bearing less TFBSs. This suggests that the post-transcriptional regulation by miRNAs is coordinated with regulation at the transcriptional level by transcription factors.

Acknowledgement CUHK: Zhang Qing NEAU: Li Yong Zhu Yanming