mRNA turnover plays a prominent role in regulation of gene expression. With the long-term goal of understanding how mRNA decay is regulated in gene expression and disease, my lab focuses on dissecting the human cellular mRNA decay machineries. mRNA degradation is regulated by activation of deadenylation, decapping or endonucleolytic cleavage followed by 5'-3' or 3'-5' exonucleolytic decay. The vast majority of the factors responsible for these activities in human cells are unknown, and our goal is to identify and characterize key human mRNA decay enzymes. This will allow research into how specific protein factors upon specific cellular cues can stabilize unstable mRNAs such as those encoding proto-oncogenes, cytokines, and lymphokines. A specific example of mRNA decay is the nonsense-mediated decay pathway which detects and degrades aberrant mRNAs, that by mutation or erroneous processing contain truncated open reading frames. Such mRNAs are recognized by a translation termination event upstream of their last exon, and they are subjected to nonsense-mediated decay. We have recently demonstrated that subunits (RNPS1 and Y14) of an exon-junction complex protein complex deposited after pre-mRNA splicing in the nucleus, communicates the position of exon-exon junctions to the translation machinery via a hUpf protein complex that interacts with the translation termination factors. The main focus of our current research is to continue our studies of the nonsense-mediated decay pathway as well as to study the role in general and regulated mRNA decay of human deadenylases and decapping enzymes that we have recently isolated.

Selected recent publications:
Lykke-Andersen J. (2002) Identification of a human decapping complex associated with the hUpf proteins in nonsense-mediated decay. Mol. Cell Biol. 22(23): 8114-8121.

Wagner, E. and Lykke-Andersen, J. (2002) mRNA surveillance: the perfect persist. J. of Cell Sci.

Lykke-Andersen, J., Shu, M-D. and Steitz, J.A. (2001) The protein RNPS1 communicates the position of exon-exon junctions to the mRNA surveillance machinery. Science, 293, 1836-1839.

Lykke-Andersen, J. (2001) mRNA quality control: Marking the message for life or death. Curr Biol., 11, R88-91.

Lykke-Andersen, J., Shu, M-D. and Steitz, J.A. (2000) Human Upf proteins target an mRNA for nonsense-mediated decay when bound downstream of a termination codon. Cell, 103, 1121-31.