Researchers at the University of Pennsylvania School of Medicine have discovered that nerve-cell dendrites have the capacity to splice messenger RNA (pre-mRNA), a process once believed to only take place in the nucleus of cells.
By uncovering this capability in dendrites, the investigators hope to relate this capacity to memory and learning, as well as cognitive dysfunction. Senior author James Eberwine, PhD, Professor of Pharmacology, and lead authors Kevin Miyashiro, and Jason Glanzer, PhD, both in Eberwine's lab, report their findings in this week's early online edition of the Proceedings of the National Academy of Sciences.
Dendrites, which branch from the cell body of the neuron, play a key role in the communication between cells of the nervous system, allowing for many neurons to connect with each other to form a network. Dendrites detect the electrical and chemical signals transmitted to the neuron by the axons of other neurons. The synapse is the neuronal structure where this chemical connection is formed, and investigators surmise that the synapse is where learning and memory occur.
Researchers have long agreed that mRNA splicing takes place within the cell nucleus. In the nucleus of a mammalian cell, a gene is copied into mRNA, which possesses both exons (mature mRNA regions destined to code for proteins) and introns (non-coding regions). mRNA splicing works by cutting out introns and merging together the remaining exon pieces, resulting in an mRNA capable of being translated into a specific protein.
The vast array of proteins within the human body arises in part from the many ways that mRNAs can be spliced and reconnected. Specifically, splicing removes pieces of intron and exon regions from the RNA, with the resulting spliced RNA often being made into protein. Should the RNA have different exons spliced in and out of it, then different proteins can be made from this RNA. The Eberwine lab was successful in showing that splicing can occur in dendrites because they have employed very sensitive technologies developed in their lab, which permits the detection and quantification of RNA splicing as well as the translated protein in single isolated dendrites.
"In addition to showing that mRNA splicing occurs in dendrites in which we added mRNA, we also detected the resulting protein," notes Eberwine. "Since the splicing machinery is present in dendrites, one could speculate that if pre-mRNA is present naturally in the dendrite, when activated, it may be spliced and translated, giving rise to many different proteins."