MicroRNAs in animal development and environmental stress

Since their discovery just over two decades ago, microRNAs have proven to be powerful, conserved regulators of gene expression, acting post-transcriptionally to shape nearly every aspect of biology. The Kim lab investigates how microRNAs control key developmental transitions, drive cellular differentiation, and enable animals to respond and adapt to environmental stress.

To uncover the molecular players that govern microRNA function, we combine genetics, genomics, proteomics, and biochemistry in the genetically tractable model organism C. elegans. This system has deep roots in the field—lin-4 and let-7, the first microRNAs, were discovered in C. elegans—and remains a premier in vivo model for dissecting the microRNA pathway. Our genome-wide RNAi screens and mass spectrometry analyses have revealed a rich set of candidate regulators and novel protein interactors of microRNA machinery that we are actively characterizing.

Current efforts focus on two major questions:

  1. How do RNA-binding proteins modulate the activity of the microRNA-induced silencing complex (miRISC)?

  2. How is microRNA regulation rewired in response to stress and aging?

Because the microRNA pathway is deeply conserved from worms to humans, our discoveries have broad relevance—including insights into diseases such as cancer, where microRNA dysfunction is a known driver of pathology.

Small RNAs in the germline: biogenesis, chromatin organization, and gene silencing

In C. elegans, endogenous small RNAs—particularly siRNAs and piRNAs—are essential for maintaining germline function. These pathways repress transposable elements, preserve heritable patterns of gene expression, and promote heterochromatin formation at specific genomic regions. Disruption of these systems has severe consequences: piRNA loss causes temperature-sensitive sterility, while defects in nuclear siRNA pathways result in progressive germline failure across generations.

Our lab studies how these small RNA pathways are regulated and why they are critical for genome defense and epigenetic control. Using genetic, molecular, and biochemical approaches, we aim to identify new components of these pathways and define their mechanistic roles in chromatin organization.

Current research focuses on the following questions:

  1. How is piRNA expression differentially regulated in male versus female germlines by the sex-specific SNPC complexes?

  2. How do siRNAs regulate chromatin remodelers to organize germline chromatin states across generations?

  3. What factors promote or inhibit the gene-silencing activity of endogenous siRNAs?

Role of non-canonical RNA binding proteins in hypoxia

RNA-binding proteins (RBPs) are essential regulators of post-transcriptional gene control. They assemble with RNAs and cofactors into dynamic ribonucleoprotein (RNP) complexes that control RNA splicing, localization, stability, and translation. Our lab has identified hundreds of novel RBPs in yeast and C. elegans—many of which are better known for roles in transcription, metabolism, or cellular trafficking. Why do these proteins bind RNA? What does that binding do?

To answer these questions, we combine classical molecular genetics and biochemistry with high-throughput crosslinking and sequencing to uncover how RBP–RNA interactions influence RNA fate.

One striking discovery: several glycolytic enzymes also act as RBPs. Under hypoxic stress, these enzymes condense into a new non-membrane-bound granule in S. cerevisiae and human liver cancer cells—structures we call Glycolytic Bodies (G bodies). Cells with G bodies consume glucose faster and show enhanced glycolytic activity, suggesting that these granules may accelerate metabolism by spatially organizing the pathway.

Our ongoing work asks:

  1. How do RNA and protein interactions drive G body assembly?

  2. What signaling pathways regulate their formation?

  3. Are these mechanisms conserved in human cells?

We’re addressing these questions using yeast, mammalian cell culture, proteomics, microscopy, and genetic manipulation to uncover how non-canonical RBPs organize cell physiology under stress.