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Cornell University

KwakLab

Department of Molecular Biology and Genetics, Cornell University

Research

RNA in phase condensates

Even after transcription, RNA has many more stages of its lifespan. It is co-transcriptionally and post-transcriptionally processed for splicing out introns, and adding poly-A tails. It gets exported out of the nucleus to start its cytoplasmic life, where translation to protein takes place.

In the cytoplasm, various mechanisms are known to control translation. We are interested in novel features of RNA that affects the amount of RNA being translated and tune the level of specific gene expression.

One hypothesis is that RNA can be redistributed into subcellular structures such as processing bodies and stress granules (SG), formed by phase separation. This redistribution can happen more extensively under stress conditions to serve as a control mechanism. We have identified hundreds of transcripts that are redistributed during endoplasmic reticulum stress, and further studying the regulation of their expression.

Outstanding questions

  • Which RNA transcripts are the targets of intracellular redistribution in cell stress?
  • Is the redistribution the cause or the consequence of translational repression?
  • What are the sequence features(cis) and RNA binding proteins(trans) regulating this?
  • FUS-RNA phase condensation
    Which other features of the RNA (e.g. poly-A tail length) contribute to this regulation?
  • What is the fate of the redistributed RNA: decay or recycle?

Approaches

  • New application of transcriptome-wide RNA dynamics and processing assays using next-gen sequencing: SG RNA-seq, TED-seq, and SLAM-seq
  • Live cell RNA imaging