Publications by Year: 2012

2012
Chen-Ching Lin*, Ya-Jen Chen*, Cho-Yi Chen, Yen-Jen Oyang, Hsueh-Fen Juan, and Hsuan-Cheng Huang. 2012. “Crosstalk between transcription factors and microRNAs in human protein interaction network.” BMC Syst Biol, 6, Pp. 18.Abstract

BACKGROUND: Gene regulatory networks control the global gene expression and the dynamics of protein output in living cells. In multicellular organisms, transcription factors and microRNAs are the major families of gene regulators. Recent studies have suggested that these two kinds of regulators share similar regulatory logics and participate in cooperative activities in the gene regulatory network; however, their combinational regulatory effects and preferences on the protein interaction network remain unclear.

METHODS: In this study, we constructed a global human gene regulatory network comprising both transcriptional and post-transcriptional regulatory relationships, and integrated the protein interactome into this network. We then screened the integrated network for four types of regulatory motifs: single-regulation, co-regulation, crosstalk, and independent, and investigated their topological properties in the protein interaction network.

RESULTS: Among the four types of network motifs, the crosstalk was found to have the most enriched protein-protein interactions in their downstream regulatory targets. The topological properties of these motifs also revealed that they target crucial proteins in the protein interaction network and may serve important roles of biological functions.

CONCLUSIONS: Altogether, these results reveal the combinatorial regulatory patterns of transcription factors and microRNAs on the protein interactome, and provide further evidence to suggest the connection between gene regulatory network and protein interaction network.

BMC Highly Accessed

Cho-Yi Chen, Shui-Tein Chen, Hsueh-Fen Juan, and Hsuan-Cheng Huang. 2012. “Lengthening of 3'UTR increases with morphological complexity in animal evolution.” Bioinformatics, 28, 24, Pp. 3178-81.Abstract

MOTIVATION: Evolutionary expansion of gene regulatory circuits seems to boost morphological complexity. However, the expansion patterns and the quantification relationships have not yet been identified. In this study, we focus on the regulatory circuits at the post-transcriptional level, investigating whether and how this principle may apply.

RESULTS: By analysing the structure of mRNA transcripts in multiple metazoan species, we observed a striking exponential correlation between the length of 3' untranslated regions (3'UTR) and morphological complexity as measured by the number of cell types in each organism. Cellular diversity was similarly associated with the accumulation of microRNA genes and their putative targets. We propose that the lengthening of 3'UTRs together with a commensurate exponential expansion in post-transcriptional regulatory circuits can contribute to the emergence of new cell types during animal evolution.

ESI Highly Cited Paper

Notably, increasing organismal complexity correlates with lengthening of the 3' UTR (Chen et al. 2012), emphasizing the importance of this region.

Turner et al, Nature Immuno (2014)

Other recent findings also support the view that UTRs may play a previously underappreciated role in establishing specific functions of tissues and organs: Throughout the evolution of animals, UTR length has increased along with morphological complexity (Chen et al. 2012).

Reyes et alProc Natl Acad Sci USA (2013)

Chen et al. (2012) ... has reported on the exponential correlation of miRNA gene number and 3'-UTR length—but not 5'-UTR or coding sequence length—with morphological complexity in animals.

Carroll et alJ Mol Cell Biol (2013)