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We are interested in the spatial control of gene expression and how interactions between RNA and the cytoskeleton influence cytoskeletal assembly. To understand the interactions between RNA and the cytosleleton there are several projects in the lab:
Identification of microtubule-localized RNAs.
We have purified microtubules from a variety of organisms (frogs, human cells, mouse ES cells, and sea urchins) and used both microarrays and Illumina sequencing to identify RNAs that are specifically enriched on microtubules. We have found that ~5% of all RNAs are specifically localized to microtubules, including novel noncoding RNAs, piRNAs, and mRNAs. We are investigating the cis acting sequences that target RNAs to microtubules and the trans-acting proteins that bind these sequences and link RNAs to the transport machinery.
Interactions between piRNAs and the cytoskeleton
Our sequencing efforts found that piwi-interacting RNAs (piRNAs) are enriched on microtubules in frog eggs and that two piwi proteins specifically interact with the cytoskeleton, suggesting that piRNA processing may be linked to cytoskeletal transport. We are pursuing how piRNAs are localized to microtubules, how the cytoskeleton influences piRNA processing, and germ cell development.
Investigating the structural role of RNA in microtubule assembly
Previous work from our group has shown that RNA is a structural component of the mitotic spindle, acting in a translation independent manner to promote microtubule assembly. We are currently characterizing how and where RNA is required for microtubule assembly as well as using a novel activity based assay to identify which RNAs are required for microtubule assembly.
Nuclease control of embryonic gene expression
Many recent studies have shown that a suite of transcription factors are responsible for mainitaining cells in a puripotent state (i.e. stem cells). Biologically the egg to embryo transition in interesting with respect to the gene expression program because a highly differentiated cell (egg) must quickly reset it's gene expression program to become pluripotent, yet little is known about this transition. We have identified a nuclease that degrades maternal mRNAs upon fertilization that is likely a key part of the mechanism that allows an egg to dramatically alter it's gene expression profile.