Immune outposts inside tumors predict post-surgery outcomes

The immune system establishes “forward operating bases”, or lymph node-like structures, inside the tumors of some patients with kidney and other urologic Read more

Hedgehog pathway outside cilia (with CBD bonus)

The Hedgehog pathway has roles in both specifying what embryonic cells will become and in guiding growing neural Read more

Tracking how steroid hormone receptor proteins evolved

When thinking about the evolution of female and male, consider that the first steroid receptor proteins, which emerged about 550 million years ago, were responsive to estrogen. The ancestor of other steroid hormone receptors, responsive to hormones such as testosterone, progesterone and cortisol, emerged many millions of years later. Biochemist Eric Ortlund and colleagues have a new paper in Structure that reconstructs how interactions of steroid receptor proteins evolved over time. This is a complex Read more

Will Hudson

Ancient protein flexibility may drive ‘new’ functions

A mechanism by which stress hormones inhibit the immune system, which appeared to be relatively new in evolution, may actually be hundreds of millions of years old.

A protein called the glucocorticoid receptor or GR, which responds to the stress hormone cortisol, can take on two different forms to bind DNA: one for activating gene activity, and one for repressing it. In a paper published Dec. 28 in PNAS, scientists show how evolutionary fine-tuning has obscured the origin of GR’s ability to adopt different shapes.

“What this highlights is how proteins that end up evolving new functions had those capacities, because of their flexibility, at the beginning of their evolutionary history,” says lead author Eric Ortlund, PhD, associate professor of biochemistry at Emory University School of Medicine.

GR is part of a family of steroid receptor proteins that control cells’ responses to hormones such as estrogen, testosterone and aldosterone. Our genomes contain separate genes encoding each one. Scientists think that this family evolved by gene duplication, branch by branch, from a single ancestor present in primitive vertebrates. Read more

Posted on by Quinn Eastman in Heart, Immunology Leave a comment

No junk: long RNA mimics DNA, restrains hormone responses

It arises from what scientists previously described as “junk DNA” or “the dark matter of the genome,” but this gene is definitely not junk. The gene Gas5 acts as a brake on steroid hormone receptors, making it a key player in diseases such as hormone-sensitive prostate and breast cancer.

Unlike many genes scientists are familiar with, Gas5 does not encode a protein. It gets transcribed into RNA, like many other genes, but with Gas5 the RNA is what’s important, not the protein. The RNA accumulates in cells subjected to stress and soaks up steroid hormone receptors, preventing them from binding DNA and turning genes on and off.

Emory researchers have obtained a detailed picture of how the Gas5 RNA interacts with steroid hormone receptors. Their findings show how the Gas5 RNA takes the place of DNA, and give hints as to how it evolved.

The results were published Friday in Nature Communications.

Scientists used to think that much of the genome was “fly-over country”: not encoding any protein and not even accessed much by the cell’s gene-reading machinery. Recent studies have revealed that a large part of the genome is copied into lincRNAs (long intergenic noncoding RNAs), of which Gas5 is an example. Read more

Posted on by Quinn Eastman in Cancer, Immunology Leave a comment