Telomerase RNP structure, biogenesis, function and regulation
The cellular reverse transcriptase telomerase adds simple-sequence repeats to chromosome ends by copying a template within its integral RNA subunit. This new telomeric repeat synthesis balances the loss of repeats that occurs with each round of genome replication. We study telomerase both in vitro, to understand its unique structure and dynamic nucleic acid handling, and in vivo, to understand the complex cellular pathways for active RNP biogenesis and regulation of telomerase action at telomeres. In parallel we are using structural, biochemical, molecular and cellular assays to investigate the assembly and regulation of human telomerase.
Beyond telomerase: biology and biotechnology of retroelements and non-coding RNAs
We have been applying our insights from studies of telomerase to investigations of retroelement reverse transcriptases and non-coding (nc) RNA biogenesis and function. In human cells we have discovered and will expand our studies of new ncRNA processing pathways and ncRNA functions in stress responses and innate immunity. We have begun to apply our understanding of telomerase to illuminate principles for non-LTR retroelement mobility and unique reverse transcriptase properties.