Gene Proximity to Nuclear Speckles Drives Efficient mRNA Splicing

Nov 7, 2024 | General news

Credits; TheScientist

Over one hundred years ago, when Santiago Ramón y Cajal observed neurons microscopically, he saw fibrillous and spotted structures inside their nuclei. Researchers later discovered that these nuclear compartments, dubbed nuclear bodies, lacked membranes but contained clusters of molecules that participated in specific functions. One such nuclear body, the speckle, contains spliceosomes that are known to be involved in mRNA splicing. Disruption of speckles leads to a range of diseases and developmental disorders, yet how speckles drive splicing remains unclear.

One idea has been that speckles are splicing factories. The splicing reaction would happen inside the speckle, and then the spliced product would leave. “What people found is that’s not what happens,” said Mitchell Guttman, a molecular biologist at the California Institute of Technology. “The reason for their highest concentration of splicing factors is very much like the same reason that, if I look for where’s the highest concentration of bed sheets in your house, it’s not going to be on your bed, it’s going to be in your linen closet, right? The location where you store them when you’re not using them. And the same was thought to be true for nuclear speckles.”

The idea that speckles might be storage sites for spliceosomes triggered Guttman to look deeper into how nuclear organization might affect the splicing process. In a recent article, he showed that when genes are preferentially positioned near speckles, mRNA splicing is significantly more efficient.

 

 

 

By Karen Kelley Perkins, PhD

Article can be accessed on: The Scientist