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Institute members discover an unexpected meeting place inside cells

Courtesy of Lewis-Sigler Institute, princeton University

09/05/13 - A group of researchers who recently joined the Institute has uncovered unusual activity in the functioning of nuclear pores, the sophisticated tunnels that shuttle proteins, RNA (ribonucleic acid), and other molecules between the cytoplasm and nucleus inside of cells. The research adds to our understanding of how DNA is organized inside cells.

Their findings, which appear in the latest issue of Molecular Cell, describe a new function for the pores. In simple eukaryotes like yeast, it has been known for some time that the pores associate with newly activated genes, and that they may function in the regulation of gene transcription. Kohta Ikegami, a postdoctoral fellow in Jason Lieb’s laboratory, began experiments with nuclear pores in C. elegans to determine if a similar function for nuclear pores existed in animal cells. What he found instead was unexpected: the pores did not function in transcription per se, but served as a meeting place for enzymes that transcribe genes into RNA and enzymes that trim the RNA.

Most protein-coding genes are transcribed by RNA Polymerase II (Pol II). RNA Pol II is equipped with a sort of “trailer” upon which it can load the RNA trimming (or “processing”) machinery. In this way, RNA processing can occur very efficiently as the message is transcribed. However, RNA Pol III lacks this trailer. The study found that core components of the nuclear pore were required for the efficient processing of a subset of non-coding RNAs called snoRNAs, and to a lesser extent tRNAs, both of which are transcribed by RNA Polymerase III. The study revealed that the nuclear pore interacts directly with RNA Pol III components and perhaps the RNA processing enzymes, allowing co-transcriptional RNA processing for this class of genes as well. The nuclear pore is a great meeting place because it is large, flexible, and importantly it is affixed to the nuclear membrane, a 2-dimensional surface that envelopes a large 3-dimensional space. A two-dimensional search for a meeting place is much easier than a search in 3 dimensions. In addition to this being a new function for the nuclear pore components, the study suggests that nuclear pores may act as meeting place for other molecular processes that require the activity of multiple enzyme complexes to be coordinated in time and space.

Illustration by Graduate Student Sophia Tintori

Illustration by Graduate Student Sophia Tintori:

In the fairy tale "Rapunzel", a prince secretly meets the beautiful Rapunzel, who is trapped by a witch in a tower, by climbing up her long hair. In this metaphor, RNA polymerase III (the prince) clambers up along DNA (Rapunzel's hair) to reach the nuclear pore (the opening in the tower), only to encounter an RNA processing enzyme (the witch with her scissors) who cleaves the transcribed RNA (depicted here as a ribbon unwound during the ascent).

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