Circadian clock meets RNA biology
Cell-autonomous circadian oscillators are generated by a set of "clock genes" that forms a transcription/translation negative feedback loop to drive and sustain molecular circadian rhythms. This molecular clock drive rhythmic expression of approximately 5-10% of mRNAs/proteins in any given tissue to ultimately drive a wide range of rhythmic biological processes in order to maintain daily cycles. But how is this achieved? What determines the correct period, phase, and amplitude?
We focus on several aspects of post-transcriptional gene regulatory mechanisms on rhythmic gene expressions. Even after transcripts are made from DNA, subsequent processing and regulatory steps determine when, where, and how much protein will be generated, and these "post-transcriptional" regulatory mechanisms add flexibility to overall gene expression. Our primary goal is to understand the roles of transcription and post-transcriptional control in generating the output rhythms of the cell in mammals.
We focus on several aspects of post-transcriptional gene regulatory mechanisms on rhythmic gene expressions. Even after transcripts are made from DNA, subsequent processing and regulatory steps determine when, where, and how much protein will be generated, and these "post-transcriptional" regulatory mechanisms add flexibility to overall gene expression. Our primary goal is to understand the roles of transcription and post-transcriptional control in generating the output rhythms of the cell in mammals.
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Poly(A) tails dynamics:
Poly(A) tail length is critical for translatability and stability of mRNAs and change in poly(A) tail length is one of the key post-transcriptional regulatory mechanisms that alter protein levels rapidly without requiring de novo transcription. By using an unique genomic technique, Poly(A)denylome analysis, recently developed by our group that can measure poly(A) tail length of each gene, we are trying to understand how changes in the poly(A) tail length drive circadian gene expression and physiology, and what is the molecular mechanisms to control rhythmic poly(A) tail length. Non-coding genes: Non-coding genes biochemically resemble conventional mRNAs, yet do not template protein synthesis. Recent genomic analyses also provided evidence that the complexity of the organism is mainly due to the noncoding portions of the genome that have regulatory potential, rather than protein-coding genes. In fact, the genome encodes at least as many non-coding genes as the known protein coding genes. We aim to understand why and how non-coding genes regulate circadian clock system. |
Adapted from Gotic and Schibler (Gene. Dev. 2012)
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