ERI Mediated Decay (EMD): Novel exonucleases and pathways in mRNA decay
Nithya Krishnan, Anand Parekh, Patrick Itotia, MingJing Wu, and
Roopa Thapar
Hauptman-Woodward Medical Research Institute and Department of Structural Biology, SUNY, Buffalo
The ERI family of nucleases are involved in a spectrum of protein-protein and
protein-nucleic acid interactions and have been implicated in an array of cellular processes:
histone mRNA metabolism, RNAi, 5.8S rRNA processing, and miRNA mediated translational repression and/
or decay. ERI-2 or Snipper (in Drosophila) are uncharacterized members of the DEDDh
subfamily of exonucleases. We recently published that Snipper1 is a highly active 35 exonuclease
in vitro and can act on both linear and double-stranded RNA substrates. A
biochemical property shared by the ERI family of nucleases is that they prefer double-
stranded RNA substrates with short 3 overhangs of 2-5 nucleotides, reminiscent of siRNAs/
miRNAs or stem-loop structures. Ongoing studies in our laboratory indicate that hERI-2
may be a RNA-Induced Silencing Complex (RISC) associated nuclease that regulates polyA binding
protein (PABP)-dependent mRNA turnover by promoting micro-RNA mediated mRNA decay. hERI-2
interacts directly with PABPC1 in vitro and in vivo. hERI-2 also co-localizes
with Ago2 but is not present in P-bodies. Microarray analysis of hERI-2
siRNA treated cells shows that it is involved in regulating the stability of a
number of cell cycle regulators, chemokines and cytokines, particularly those with AU-rich elements
in their 3 untranslated regions. Three mRNAs implicated in disease states that are targeted
by hERI-2 are the cyclin inhibitor and tumor suppressor CDKN1A, the chemokine CCL5,
and the cytokine IL-8. ERI-2 also regulates the cell cycle. Ongoing studies
on both ERI-1 and ERI-2 to understand the functional and structural roles
of these nucleases in mRNA decay of specific mRNA targets will be presented.
1.Kupsco, J.M., Wu, M.J., Marzluff, W.F., Thapar, R., and Duronio,
R.J. Genetic and biochemical characterization of Drosophila Snipper: A promiscuous member of the
metazoan 3hExo/ERI-1 family of 3 to 5 exonucleases. RNA (2006), 12(12): 2103.