Sheffield Institute for Nucleic Acids

Gene expression

Ribonucleic Acid (RNA) is an amazingly versatile molecule which can fold into a wide variety of shapes often in conjunction with proteins to make molecular machines. RNA performs a bewildering array of functions in the cell ranging from the control of chromosome structure and activity through to its function as both the template and machine for protein synthesis. The recent discovery that the majority of the human genome is transcribed further highlights the central role that RNA plays in the life of a cell.

In the Institute we are particularly interested in how RNA is made in eukaryotic cells through the process of transcription and how it is subsequently processed to produce functional RNA molecules in the cell. We are interested in how the cell couples RNA production and processing steps to ensure high fidelity and efficiency in these processes. We are also investigating how RNAs are sorted between the nucleus and cytoplasm and how the cell knows when an RNA is ready for export.

The production and processing of mRNA are coupled through transcription

The role that RNA plays in human disease is becoming increasingly apparent with the discovery that many of the genes, which cause genome instability when mutated, are proteins involved in the production/processing and activity of RNA. Furthermore neurodegenerative disorders such as motor neuron disease frequently involve mutations in RNA processing factors or mutations that lead to aberrant export of unprocessed pre-mRNAs. We are working with colleagues in SITRaN to establish the molecular basis for motor neuron disease which in turn may guide efforts to develop treatments in the future.

In summary, we are particularly interested in the following areas of RNA biology:

  • Transcription termination and polyadenylation
  • Coupling transcription with RNA processing
  • mRNA export processes
  • How nuclear RNAs such as long non-coding RNAs (lncRNAs) are retained in the nucleus
  • RNA quality control by the exosome
  • The epitranscriptome and RNA methylation.
  • RNA mediated DNA damage through defects in RNA packaging and R-loop formation
  • MicroRNAs and their role in cancer and development
  • Enhancer RNAs and chromatin modifications
The assembly of mRNA export factors (green) on the periphery of nuclear speckles (red) in human cells revealed using bifluorescence complementation.