Standing guard between a cell's nucleus and its main chamber, called the cytoplasm, are thousands of behemoth protein structures called nuclear pore complexes, or NPCs. NPCs are like the bouncers of a cell's nucleus, tightly guarding exactly what goes in and out. Each structure contains about 1,000 protein molecules, making NPCs some of the biggest protein complexes in our bodies. One of the most notable clients of NPCs is a class of molecules known as messenger RNAs, or mRNAs. These are the messengers that carry genetic instructions from the nucleus to the cytoplasm, where they are then translated into proteins.
But how the NPC transports the mRNAs out of the nucleus is still a mystery.
MRNAs - Cargoes - NPCs - Process - Fraction
"The mRNAs are one of the largest cargoes carried through NPCs, and the whole process occurs in just a fraction of a second," says André Hoelz, professor of chemistry at Caltech, a Heritage Medical Research Institute (HMRI) Investigator, and a Howard Hughes Medical Institute (HHMI) Faculty Scholar. "How this works has been one of the greatest unsolved problems in biology."
NPCs are associated with several diseases. Mutations to proteins within the complex have been linked to motor neuron diseases such as amyotrophic lateral sclerosis (ALS), and people with Huntington's disease are known to have defects in the function of their NPCs.
Study - June - Issue - Nature - Communications
In a new study in the June 13 issue of Nature Communications, Hoelz and his group—spearheaded by Daniel Lin (Ph.D. '17), a former graduate student at Caltech now at Whitehead Institute for Biomedical Research at MIT, and Sarah Cai, an undergraduate student at Caltech—report the first atomic-scale look at the specific components of human NPCs responsible for dropping mRNAs off in the cytoplasm. For an mRNA to be transported through an NPC, it must be tagged with a nuclear export factor, a type of small protein. That tag...
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