Biological complexity: nuclear membrane pore controls (Introduction)

by David Turell , Wednesday, June 27, 2018, 23:37 (2341 days ago) @ David Turell

These pores are highly complex:

https://evolutionnews.org/2018/06/how-the-nucleus-guards-its-gates/

"The nuclear pore complex (NPC), which we mentioned briefly here and here, has been a prime target of research for years now, ever since biochemists realized how large it is and the vital role it plays guarding what moves in and out of the nucleus. The NPC has to validate cargo large and small through its hoop-like opening with dangling ends that resemble a basketball net.

"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.

"Moreover, the article goes on to say, mRNAs, though being one of the largest cargoes ferried through the NPC, make it through the whole process in a fraction of a second.

***

"The NPC has tags of its own. A molecule can’t get through without a ticket.

"In a new study in the June 13 issue of Nature Communications, Hoelz and his group… 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 is like a ticket that allows the mRNA to enter the central transport channel of the NPC. Once the mRNA reaches the cytoplasmic side, it must surrender the ticket — otherwise, the mRNA could travel back into the nucleus, and the proteins it encodes wouldn’t get made.

"It was enough of a challenge to figure out that one step, how the ticket is surrendered. To study it, they had to figure out the crystal structure of human Gle1, an essential component of the NPC validation system. Unlike its counterpart in yeast, Gle1 was found to be stabilized by Nup42, one of dozens of “nucleoporin” (Nup) proteins. Another protein named DDX19 un-tags the molecule as it exits.

"The scientists marveled that yeast Gle1 was almost identical to human Gle1. Caltech offers rotating images of the proteins. They’re hard to tell apart.

***

"Strikingly, the Gle1CTD•Nup42GBM interaction mechanism is virtually identical in species separated by more than a billion years of evolution.

***

"The flow of genetic information requires newly transcribed and processed mRNAs to be exported from the nucleus to the cytoplasm through nuclear pore complexes (NPCs). NPCs are massive macromolecular machines perforating the nuclear envelope, each composed of ~1000 protein subunits (collectively termed nucleoporins) totaling to a molecular mass of ~120 MDa in humans. By fusing the inner and outer nuclear membranes, NPCs create pores through the nuclear envelope and simultaneously generate a passive diffusion barrier composed of disordered protein sequences enriched in phenylalanine-glycine (FG) repeats. Each NPC is composed of a ~60 MDa symmetric core that is decorated by different proteins on its nuclear and cytoplasmic faces, which are referred to as the nuclear basket and cytoplasmic filament nucleoporins, respectively.

"Preparation of mRNAs for nuclear export is a highly coordinated process that begins co-transcriptionally and results in the addition and removal of mRNA-binding proteins during transcription and nuclear processing until an export-competent messenger ribonucleoprotein particle (mRNP) is formed.

***

"Multiple levels of quality control can be seen in action here. The ticketing process begins as the gene is transcribed. It is re-checked by “nuclear processing” inside the nucleus. Only when the mRNA is “export competent” can it pass the NPC. As it passes through, its ticket is removed, so that it cannot return. “This spatial regulation of activity prevents re-import of mRNPs into the nucleus, and thus ensures the directionality of mRNA export.” The NPC has all the marks of a programmed system with built-in quality control. It is very rapid, working in just fractions of a second. It’s even environmentally friendly; all the parts are recycled. And there are thousands of these little factories in each nuclear envelope. Then there’s this minor miracle of coordination: at cell division, the entire nuclear envelope, with all its NPCs, is torn down and reconstructed.

Comment: Try to deny this system is not designed. Look at the article to see the NPC diagram.