Making a movie at the molecular level? A new method of imaging molecule-sized machines as they do the complex work of cutting and pasting genetic information inside the nucleus is the subject of a just-published paper in the journal Science, and the movies have revealed a surprise about how the process works: these critical assembly pathways are a two-way street. This new knowledge could help scientists better understand how the process works in normal cells—and what can go wrong in cancer cells.
Melissa J. Moore, PhD, Howard Hughes Medical Institute Investigator and professor of biochemistry & molecular pharmacology, with colleagues at Brandeis University and Columbia University, has long been studying the spliceosome, a complex of specialized RNA and protein subunits that acts as molecular scissors and tape during gene transcription. The spliceosome snips out the nonsensical sections of genes and stitches the remainder back together to create the final cellular blueprints for making every protein. Without this cutting and pasting—called RNA splicing—the amount of genetic information that each gene could contain would be strikingly limited. Because of alternate splicing patterns that produce alternate blueprints, each one of our genes can code for multiple proteins; hence the critical importance of the spliceosome.
“Understanding how these micro-machines function inside the cell is important for many reasons,” said Aaron A. Hoskins, PhD, a post-doctoral fellow in Dr. Moore’s lab and first author of the Science paper. “One is to further decipher basic biology—what makes us humans—and another is to understand how diseases related to these different machines come about.” The paper, “Ordered and Dynamic Assembly of Single Spliceosomes,” appeared in the March 11 issue of Science and caps a five-year collaboration of three research laboratories (Moore Lab
, UMASS; Cornish Lab
, University of Columbia; Gelles Lab
, Brandeis University) with remarkably diverse expertise. The UMass Medical School Communications full-length press release can be found here