Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression

New research from a transatlantic collaboration between Weill Cornell Medicine and Karolinska Institutet scientists suggest that genetic differences in ribosomal DNA may affect the way a ribosome is assembled and subsequently how it builds proteins.

"The millions of ribosomes in our cells, which translate the genetic code carried by our DNA into proteins, have long been thought to all be identical in every cell, like a manufacturing plant with rows and rows of the same machines building the same product. Our collaborative research suggests that genetic variation in the most essential component of the ribosome, ribosomal RNA, may influence the composition of the ribosome and how much and which proteins are made", says Theresa Vincent, Assistant Professor at the Department of Physiology and Pharmacology at Karolinska Institutet.

This finding could explain why ribosomal genes have been linked to developmental disorders and cancer progression.

Dr. Scott Blanchard in collaboration with Theresa Vincent analyzed ribosomal DNA from thousands of individuals to find that each person actually contains a wide variety of ribosomes. They also found that rDNA sequences vary from one person to the next and that these variants are found in regulatory functional centers of the ribosome. Importantly, rRNA variants were expressed in translating ribosomes and in a tissues specific manner such that the brain, ovaries, liver and lung all expressed different variants.

Their findings provide concrete evidence of pervasive variation in the ribosomal DNA genes that encode ribosomal RNA. These genes have proved very difficult to analyze, and thereby constitute a largely unexplored area of the genome or popularly referred to as the “dark matter” in the genome.

These collaborative efforts provide a new and unanticipated critical framework for exploring the possibility that the expression of genomically encoded variant rRNA alleles can give rise to functionally heterogeneous ribosomes that directly, contribute to human health and disease such as cancer.

For therapeutic purposes this existence of genomically encoded specialized ribosomes may open up a new avenue of drug development where specific targeting of subpopulation of ribosomes is made possible in different disease states such as cancer.

The breakthroughs presented in their study have recently been published online in Science Advances.