It’s axiomatic that the double-stranded DNA molecule is the key to life — containing the entire genome for every organism. But without RNA, that information couldn’t do much: RNA is both the bridge between DNA and the proteins that carry out the functions of life and the toolbox that helps those proteins do their work. It exists in a variety of forms, each with a particular role and purpose, not all of which are fully understood. Penn scientists are at the forefront of exploring and pushing back the boundaries of the bewilderingly complex and fascinating world of RNA.
GUARDIAN OF THE TRANSCRIPTOME
As messenger RNA is transcribed from DNA to carry genetic information out of the nucleus, non-coding genes need to be removed from the RNA strand and the remaining pieces spliced together. This is the function of the spliceosome, comprised of specialized bits of RNA and proteins called snRNPs. Studying these RNAs and the problems that can arise when their work is disrupted is one of the specialties of Gideon Dreyfuss, PhD, professor of Biochemistry and Biophysics and a Howard Hughes Medical Institute investigator, and his lab. Dreyfuss discovered that one of the snRNPs of the spliceosome has another important function, namely serving as the “guardian of the transcriptome” by preventing the premature termination of the mRNA transcription process. His lab also studies a protein complex called SMN (survival of motor proteins) involved in the creation of snRNPs that’s also been linked to a neuromuscular disorder, spinal muscular atrophy. Read More.
RNA AND NEUROLOGICAL DISORDERS
Misfolded RNA-binding proteins have been implicated in various neurological disorders, such as Parkinson’s, Alzheimer’s, and Huntington’s disease. Probing these connections is a major research focus of the lab of James Shorter, PhD, associate professor of Biochemistry and Biophysics. He discovered that mutations in prion-like segments of certain RNA-binding proteins are associated with a form of ALS (amyotrophic lateral sclerosis) and other neurodegenerative conditions. Read more.
ALTERNATE RNA SPLICING
The transcription of DNA into mRNA isn't always as straightforward as was once thought, with each gene encoding a single protein. The phenomenon of alternative splicing – where a single gene can encode multiple proteins – was discovered over 30 years ago. Kristin Lynch, PhD, associate professor of Biochemistry and Biophysics, focuses on identifying and understanding the specific mechanisms and patterns of alternative splicing: how it happens during the transcription process and its ultimate physiological effects, both good and bad, particularly with regard to the immune system. Read more.
RNA AND THE RIBOSOME
After messenger RNA is transcribed from DNA inside the nucleus, it's transported out of the nucleus through the cell cytoplasm to the ribosome, the molecular machine that translates the genetic message into proteins. But the details of how the ribosome accomplishes that job with the necessary painstaking fidelity are still not fully understood. The research of Yale E. Goldman, MD, PhD, professor of Physiology, and Barry S. Cooperman, PhD, professor of Chemistry, zeroes in on the secrets of the ribosome, using innovative techniques such as single-molecule fluorescence and optical traps to capture and study the ribosomal machinery at work. Read more.
James Eberwine, PhD, professor of Pharmacology, approaches the RNA world from a different direction: His lab looks not at how RNA functions inside the nucleus or ribosome, but how it can behave in other ways and places in the cell that can profoundly affect a cell’s function or even its identity. He has found that RNA splicing -- the crucial modification of mRNA before its translation into proteins -- isn't something limited strictly to the nucleus. Editing can occur elsewhere, such as in nerve-cell dendrites, at the very tips of these long neuronal extensions. Read more.