Department of Biology
Pennsylvania State University
208 Mueller Lab
University Park, PA 16802
2008 Searle Scholar
Evolution of Gene Networks Regulated by small RNAs
What are the characteristics of small RNA genes in different genomes?
Plant small RNAs are classified as either small interfering RNAs (siRNAs) or microRNAs (miRNAs). Identification and functional analyses of miRNAs have proceeded rapidly in multiple plant species. However, the majority of expressed small RNAs in any plant species are clearly not miRNAs -- progress in understanding these "orphan" small RNAs has been much slower. We have developed a methodology for the systematic study of siRNA genes, and are currently pursuing genome-wide analyses in multiple plant species.
Two classes of non-miRNA small RNA loci in the moss P. patens. Loci in blue are dominated by 21nt small RNAs (panel A), tend to be short (panel C), and are often asymmetrical with respect to the genome, indicating origins from single-stranded precursors. In contrast, the loci in red are typified by a remarkably consistent ratio of 21nt, 23nt, and 24nt small RNAs (panel B), tend to be much larger (panel C) and have approximately equal distributions from both genomic strands -- indicative of birth from a double-stranded RNA.
What are the regulatory targets of small RNAs in various species?
Small RNAs, whether siRNAs or miRNAs, act by directing the repression of target genes. Thus, finding the targets of small RNAs is essential for understanding their functions. Much of our current effort is aimed at combining computational target predictions with experimental evidence to determine the targets of small RNAs from various species. Our recent work has shown that homologous miRNAs target homologous genes in widely diverged species. In other cases, miRNAs which are not as widely conserved nonetheless target homologous genes in long diverged species, indicating recurrent evolution of miRNA functions. Our ongoing work seeks to extend the maps of confirmed small RNA-target interactions in many more plant species.
Conservation of miRNA targets between Arabidopsis thaliana and Physcomitrella patens. Confirmed miRNA complementary sites are shown in red in the context of the target mRNAs (to scale).
April, 2009: Profiled as a "Scientist to Watch" in The Scientist (Vol. 23, issue 4, p. 62)
November, 2009: Nominated for the C.I. Noll Outstanding Teaching Award by my academic department. Award decision for this College-Wide Award is pending.
How can we account for the extreme conservation of some small RNAs and their regulatory targets in long diverged species?
To answer this question we have adopted the moss Physcomitrella patens as a companion model organism to Arabidopsis thaliana. P. patens is genetically tractable, transformable by homologous recombination, and has a completely sequenced and assembled nuclear genome. We are a) creating P. patens mutants compromised in various small RNA genes, and b) assessing the functions of homologous miRNAs in both P. patens and A. thaliana using molecular and genomic techniques. These experiments aim to understand how the use of conserved molecular switches (e.g. the ancient miRNA/target interactions) has been maintained intact for hundreds of millions of years of land plant evolution.