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Structure and function of non-coding RNAs
The functions of RNA extend far beyond coding for amino acid sequences. My research group is interested to elucidate how non-coding RNAs function by forming defined three-dimensional structures and by interacting with proteins. In particular, we are investigating how a class of small RNAs (called microRNA or miRNA) is processed and used as guides for target recognition in RNA interference. The projects will be investigated using X-ray crystallography, biochemistry and in vitro evolution methods.
MiRNAs are involved in many important biological functions. The expression of some miRNAs has recently been demonstrated to correlate with cancers. They regulate the expression of many protein-coding genes by targeting their messenger RNAs (mRNAs) for cleavage or translational repression. To become the short mature functional forms, the long primary transcripts (pri-miRNAs) need to be specifically recognized and cleaved by a series of dedicated cellular processing factors. In this sense, it is this series of processing machinery that determines which RNAs out of the large number of RNA molecules existing in both the nucleus and cytoplasm are processed into mature miRNA. The first step of this processing pathway involves two protein factors, Drosha (a ribonuclease III family member) and DGCR8 (an RNA binding protein). We are characterizing the RNA binding and cleavage properties of these proteins, in the hope to use the knowledge to improve the algorithms to predict new miRNA genes and to design gene knockdown technologies by mimicking pri-miRNA.
