Cancer and other genetic diseases stem from faulty gene expression, which is regulated by many factors including micro-RNAs (mRNAs) and primary-mRNAs (p-mRNAs). In the nucleus of every cell, mRNAs are recognized by the Microprocessor complex, which is an enyzme made up of a DROSHA protein and two DGCR8 proteins. Despite the importance of this complex, it has been poorly understood due to the lack of any information on the structures of its proteins. Now, scientists from the Institute for Basic Science have obtained the three-dimensional crystal structure of DROSHA in order to help further understand the elusive Microprocessor complex.

The findings revealed that DROSHA has two DGCR8-binding sites and a unique "bump" in its structure, painting a clear picture of how the Microprocessor is composed. Furthermore, the team was able to determine how DROSHA and DGCR8 interact together in order to determine where p-mRNA is cut and processed in the nucleus.

The scientists also noted that the structure of DROSHA is very similar to the Dicer enzyme, despite the fact that these two enzymes do not work in proximity to each other, leading them to hypothesize that DROSHA might have evolved from a homologue of the Dicer enzyme.

The findings uncover a great deal of information on DROSHA's structure, which is an essential step in further understanding mRNA biogenesis and how these various pieces of the puzzle can malfunction to initiate genetic diseases such as cancer. This knowledge will help scientists create new ways of regulating gene expression and stopping tumor growth.

"In the future, we are planning to solve the structure of pri-miRNA-bound Microprocessor complex," Sung Chul Kwon, who participated in the research, said in a press release.

The findings were published in the Dec. 28 issue of Cell.