The central dogma of biology defines the flow of genetic information: It describes how proteins are made from mRNA templates, which are in turn made from DNA. Exporting the mRNA from inside the nucleus to the site of protein translation in the cytoplasm is a critical step for life for eukaryotes like us.
Yi Ren’s most recent paper, published in eLife, describes the structure of a protein complex involved in mRNA export that sheds light on the underlying molecular mechanism of mRNA export and the role it plays during infection by herpes viruses. Ren is an assistant professor in the Department of Biochemistry.
“Human cells carry tens of thousands of mRNAs. How does the cellular machinery handle such a diverse population of molecules and transport them from the nucleus where they are synthesized to the cytoplasm for protein translation?” she asked.
This is more than just an idle question. Understanding mRNA export is important not just for scientists to understand our cells’ own functioning but is also critical from an infectious disease point of view. mRNA nuclear export is targeted by a variety of viruses to block host gene expression and immune response and/or promote viral gene expression. The Ren lab has previously shown that this is the case for the influenza A virus, the only known type of influenza that can cause flu pandemics, and SARS-CoV-2, the virus that causes COVID-19. Their latest research suggests that herpes viruses might also belong on that list.
The toll of these viral infections worldwide is almost unimaginable. Influenza alone causes about a billion cases worldwide each year. COVID-19 has caused, on average, almost 200 million cases annually since its emergence in 2020. And herpes simplex virus 1, which causes oral herpes and is incurable, affects nearly half of the world’s population.
In the paper, first author Bradley Clarke and coauthors describe key steps in the mRNA nuclear export pathway and explain how the cellular machinery engages with newly synthesized mRNA.