June 12, 2019
National Institute of Information and Communications Technology
Osaka University

Press Release
Nuclear pore complex outer rings: no longer “one size fits all”
A team led by researchers from Osaka University and NICT finds that, contrary to popular belief, theouter rings of eukaryotic cell nuclear pore complexes are asymmetrical rather than perfectly identicalIn eukaryotic cells, the nucleus is walled off from the rest of the cell by the nuclear envelope.
All transport into and out of the nucleus occurs via cylindrical channels called nuclear porecomplexes (NPCs) that penetrate the nuclear envelope. Each NPC is made up of eightrepeating protein complexes containing at least 30 different types of proteins, called
nucleoporins (Nups). These complexes fit together like the wedges of an orange, leaving achannel in the middle through which proteins, RNA, and signaling molecules can betransported.
The Nups at either end of the NPC form ring-like structures that frame the openings of thechannel. So far, all work in eukaryotic cells has suggested that these outer rings are identical,
comprising equal numbers of nine or ten different Nups linked together in repeating Yshaped structures.
But in a study published this week in PLoS Genetics, a team lead by researchers fromOsaka University and the National Institute of Information and Communications Technology(NICT) found that the “one size fits all” theory may not hold true.
“We wanted to take a closer look at the NPCs of fission yeast, Schizosaccharomyces
pombe,” says lead author of the study Haruhiko Asakawa at Osaka University. “Like othereukaryotes, S. pombe has a conserved set of Nups, but unlike these other species, the outerring structures are made up of unequal numbers of the different types of proteins.”
And while the researchers were expecting some differences, they weren’t quite prepared forthe completely divergent structures revealed by using high-powered immunoelectron andfluorescence microscopes. By carefully tracking the locations of the different proteins, they
made their startling discovery.
“It’s like S. pombe has completely thrown the rule book out the window,” laughs seniorauthor Tokuko Haraguchi at NICT. “We found that the proteins that make up the outer ring
structures were arranged asymmetrically. Rather than having identical structures, thenuclear outer ring comprised only two types of Nups, with the seven remaining Nups all partof the cytoplasmic outer ring structure.”Interestingly, the researchers found that the asymmetrical ring structure was essential fornormal cell growth in S. pombe.
“This diversity in the outer ring structures may provide clues as to how the nuclear pore isformed, along with insights into the structure and function of the cell nucleus from an
evolutionary point of view,” says Asakawa. “We also hope that our findings will help us tobetter understand the mechanisms of diseases caused by abnormal nuclear pore proteins,which in turn may lead to new treatment strategies.”

Fig 1. Schematic of the nuclear pore complex.
The nuclear pore complex is an eight-fold rotational symmetric cylindrical structure
penetrating the nuclear membrane. Molecular transport between the nucleus and thecytoplasm takes place by passage of molecules through the interior of the tubularstructure. The outer ring structure is a ring-like structure which is found on both the innerand cytoplasmic sides of the nuclear pore complex in humans and budding yeast.

Fig 2. Schematic drawings of the outer ring complex and the NPC structurein H. sapiens (left) and S. cerevisiae (middle) in comparison to that in S. pombe (right).

The article, “Asymmetrical localization of Nup107-160 subcomplex components within thenuclear pore complex in fission yeast,” was published in PLoS Genetics at DOI:
https://doi.org/10.1371/journal.pgen.1008061.

< Contact >Yasushi Hiraoka, Haruhiko Asakawa
Graduate School of Frontier Biosciences
Osaka University
Tel: +81-6-6879-4620, 4621
Fax: +81-6-6879-4622
E-mail: hiraoka@fbs.osaka-u.ac.jp, askw@fbs.osaka-u.ac.jp
Tokuko Haraguchi
Frontier Research Laboratory
Advanced ICT Research Institute
NICT
Tel: +81-78-969-2241
Fax: +81-78-969-2249
E-mail: tokuko@nict.go.jp
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