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Oct 16

Research Bit: Nuclear pore proteins as regulators of gene expression

Research Bits
The Packard Center welcomed Maya Capelson from the University of Pennsylvania to a recent Investigator's meeting.

Meeting Date: October 16, 2020

Presenter: Maya Capelson

Talk Title: Nuclear pore proteins as regulators of gene expression


What was the question being asked?

How do nuclear pore proteins regulate the expression of genes in aging cells?

Why is this important for ALS research?

In the last five years, several of the genetic mutations that lead to ALS have been shown to directly alter the composition and/or function of the nuclear pore complex (the large protein “gate” that connects the nucleus to the cytoplasm in cells). However, many of the proteins that comprise the nuclear pore complex have additional roles in the interior of the nucleus. To fully understand how the absence or improper localization of these proteins may contribute to disease, we must account for ALL their functions.

What was the take-home message?

Ecdysone inducible genes (a subset of genes present in fruit flies) exhibit transcriptional memory. This means that at the molecular level, a second stimulus leads to a much stronger response than the first. This “memory” is at least partially facilitated by the nuclear pore protein Nup98, which is a protein that exists in close proximity to the nuclear pore complex, as well as at promoter and enhancer sites within the nucleoplasm. Different nucleoporins appear to regulate the transcription of different genes, providing even more complexity to how their alteration in disease (such as ALS) may contribute to the progression of that disease.

How do you think the results of this study might impact future approaches to the treatment of ALS?

This work provides motivation to more deeply investigate all the functions of proteins that are affected by disease, not just their most well-known or prominent function. Over time, this method of investigation will lead to a more comprehensive understanding of the cellular processes that are altered in ALS.


Prepared by:

Ben Zaepfel
Ph.D. Candidate | Rothstein Lab
Johns Hopkins University

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