Protein Editing - A Lesson in Scientific Discovery

With a recently published scientific report on unusual protein activity gathering publicity in academic circles, Morgan Morris explains why it is significant and how the study impacts our understanding of biology at a cellular level

Biology is a diverse and oftentimes confusingly divergent field of science, encompassing everything from taxonomy to toxins, conservation to cancer cells and pollination to the pancreas. For this reason, then, scientists take some comfort in a few long established theories: all organisms are composed of a cell or cells, for example, and all life evolves via natural selection. Yet according to a report recently published in the journal Science on January 2nd, one of the most fundamental principles of biology regarding proteins may have to be reconsidered and reassessed entirely.

Proteins are essential biomolecules without which life as we know it could not exist. Any good textbook tells us that the only thing in our bodies- indeed, in any organism- which has the information to make proteins is our genes, contained within our DNA. Ribosomes take this information and link small molecules called amino acids (of which there are 20) into a chain. This forms the protein encoded by the gene in question. However, a team of researchers based in the University of Utah have recently discovered a particular protein which can make another protein without any interference from our genes at all.

The protein in question is called Rcq2 and part of a “quality control team” which repairs the damage when our ribosomes malfunction.  The amino acids may have been joined together in the wrong order or even incorporated into a chain where they are not needed. When this happens, the ribosome stops and the quality control team intervenes. A research team, led by Peter S. Shen, a biochemistry postdoctoral fellow in the University of Utah and California, Jonathan S. Weissman, professor of cellular pharmacology and biochemistry at the University of San Francisco, Onn Brandman, assistant biochemistry professor at Stanford University, and Adam Frost, adjunct professor of biochemistry at the University of San Francisco, studied how the protein Rcq2 actually works.

Using cryo-electron microscopy, researchers literally froze cells in the process of correcting ribosomal errors. The results showed that Rcq2 bound to the ribosomes had the possibility to add on amino acids to halted proteins because the Rcq2 was itself also bound to tRNAs, which are a form of nucleic acid that carry amino acids. In addition, it was observed that the halted proteins had vast chains of 2 amino acids- alanine and threonine- added on in a random sequence. The ground breaking conclusions drawn were that the Rcq2 protein was responsible for adding on these extra 2 amino acid chains to faulty proteins, and was doing so independently of instructions from DNA.

The reasons for why Rcq2 adds on these amino acids randomly is not yet well understood. However, theories include that it acts as a test of ribosome functionality and that the random alanine-threonine sequence may signal for destruction of the dysfunctional protein overall. The future of research into this unconventional protein will most likely seek to answer fundamental questions of where and when the protein chain is lengthened within the cell. As well as this, it is not yet actually known what would occur if both the ribosome and the Rcq2 protein malfunctioned, leaving the open question of whether or not other similar proteins exist within cells that can independently modify and mould proteins and which act as potential “back up”.

As it stands, the research serves as an invaluable insight into just how little we humans understand of the complexity of biological systems and how our scientific knowledge is an ongoing and ever changing process of inquiry and observation. Co-senior author Dr. Brandman of Stanford University was quoted as saying, “There are many interesting implications of this work and none of them would have been possible if we didn’t follow our curiosity…the primary driver of discovery has been exploring what you see, and that’s what we did. There will never be a substitute for that.”