Exploring the unknowns of gene expression control: Post-transcriptional regulation

Our interest is the understanding of post-transcriptional regulatory networks that control gene expression. The birth of mRNA depends on transcriptional regulation, however, the fate of mRNA is determined by a series of post-transcriptional regulation. Newly synthesized mRNAs are under the control of translation, stability, and subcellular localization, which governs spatial and temporal changes of protein synthesis. The post-transcriptional regulation maintains molecular and cellular homeostasis and plays a critical role in many cell types, especially at synapses in neurons, at the leading edge of migratory cells, and in oocytes and early embryos. Moreover, deregulation and failed coordination of these mechanisms contribute to the developmental defects and pathological conditions.

The most important factors that orchestrate the post-transcriptional regulation are non-coding RNAs and RNA binding proteins. Various kinds of non-coding RNAs, including microRNAs, and more than a thousand RNA binding proteins have been identified so far, and they are known to form a complex together with the target mRNAs through dynamic interactions, which functions as a key regulator of gene expression. But, it still remains largely unknown how they specifically interact to build the regulator module with a certain function and how those regulatory modules control the gene expression and affect the biological processes. We expect to decode post-transcriptional regulatory networks by studying systematically the action mechanism and function of non-coding RNAs and RNA binding proteins.

Research topic III: Localized translation

Some mRNAs are specifically localized in a particular subcellular region, facilitating the spatial control of translation to produce a restricted distribution of the protein. Localized translation presents several significant advantages; lowers the transport cost of the protein, prevents malfunctioning of ectopic proteins at the inappropriate site, supports the efficient incorporation of proteins into macromolecular complexes, and provides fine-tuning of gene expression in both space and time. Localized translation control has been studied in asymmetric cells and established as the underlying mechanism to control cell migration, neuronal maturation, and embryonic patterning. Recently, organelle-coupled translation using localized mRNAs has been highlighted as a relevant mechanism to supply the proteins and form a complex which are required for the proper function and maintenance of organelle. We are studying the molecular mechanism of mitochondria-localized translation and its effect on mitochondrial dynamics and metabolism in adipocyte browning.