Leslie Sieburth's Lab Page
Leslie Sieburth's PubMed Literature Search
My lab focuses on mRNA decay and long-distance signaling pathways using the plant model system Arabidopsis. Specifically, we are studying the roles of P-bodies and mRNA decapping for control of gene expression (RNA level and translational regulation), and a novel signaling pathway used to coordinate developmental processes over long distances.
Analyses of developmental mutants led to identification of mutants with defects in the mRNA decapping enzyme (DCP2/TDT), and mutants with defects in the P-body scaffold protein (VCS/Ge-1/HEDLS). The biochemical reactions leading to removal of an mRNA's 5' cap occur within small cytoplasmic foci called P-Bodies (see figure). The traditional view holds that mRNA decapping and 5' to 3' decay is a bulk pathway that is largely redundant with exosome-mediated 3' to 5' decay. However, our work in Arabidopsis indicates that each of these pathways has specific mRNA substrates (Goeres et al., 2007). These findings lay the groundwork for identifying the determinants that specify an mRNA for a particular pathway.
In plants, microRNAs (miRNAs) have largely been assigned roles in cleavage of their target mRNA, although a few examples of miRNA-directed translational arrest have been documents. We have recently shown that miRNA-directed translational arrest is a wide-spread phenomenon in plants, and that it requires P-bodies (Broderson et al., 2008).
We have also uncovered natural suppressors of mRNA decapping mutants (Goeres et al. 2007). A tremendous resource in Arabidopsis is a large collection natural accession with considerable genetic variation. We find that mRNA decapping mutants show different phenotypes in specific accessions, and we are exploiting this resource to identify the suppressors. We have identified at least two suppressors genetically, and these suppressor function at the RNA level to modify RNA accumulation profiles.
Research in our lab has uncovered a novel long-distance signaling pathway that uses a novel carotenoid-derived signal (possibly something like retinoic acid). This pathway was identified by characterization of a mutant, bypass1, which over-produces the signal. BYPASS1 encodes a protein of unknown function, and with no functionally characterized domains, but genetically it acts as a negative regulator. How the signal modifies normal development is unknown, but microarray analyses show that the signal is sufficient to drastically reprogram transcription in tissues distant from the signal. Current work in the lab is focused on identifying the signal using biochemical and metabolomic approaches, identifying targets of the signal using molecular, genetic, and cell-biology approaches, and determining how BPS1 functions in the cell. We believe these efforts will allow us to assign the bps1 mobile signal as a new plant hormone.
Both the RNA decay and the bps1 long-distance signaling mutants affect normal leaf development. Our long-term goal is to understand how these processes, and other pathways, function in specifying normal development of leaves.
P-body components TDT and VCS interaction and P-Body Formation. Top: The TDT/DCP2 and VCS proteins interact in yeast. Bottom: TDT/DCP2 localizes to discrete cytoplasmic foci, and this localization requires VCS.