Drosha

Drosha is a Class 2 is_associated_with::ribonuclease III is_associated_with::enzyme that in humans is encoded by the DROSHA (formerly RNASEN) is_associated_with::gene.

Function
Members of the ribonuclease III superfamily of is_associated_with::double-stranded (ds) is_associated_with::RNA-specific is_associated_with::endoribonucleases participate in diverse is_associated_with::RNA maturation and decay pathways in is_associated_with::eukaryotic and is_associated_with::prokaryotic cells. The RNase III Drosha is the core is_associated_with::nuclease that executes the initiation step of is_associated_with::microRNA (miRNA) processing in the nucleus.

The microRNAs thus generated are short is_associated_with::RNA molecules that regulate a wide variety of other genes by interacting with the is_associated_with::RNA-induced silencing complex (RISC) to induce cleavage of complementary is_associated_with::messenger RNA (mRNA) as part of the is_associated_with::RNA interference pathway. A microRNA molecule is synthesized as a long RNA is_associated_with::primary transcript known as a pri-miRNA, which is cleaved by Drosha to produce a characteristic is_associated_with::stem-loop structure of about 70 is_associated_with::base pairs long, known as a pre-miRNA. Drosha exists as part of a is_associated_with::protein complex called the Microprocessor complex, which also contains the double-stranded RNA binding protein Pasha (also called DGCR8). Pasha is essential for Drosha activity and is capable of binding single-stranded fragments of the pri-miRNA that are required for proper processing.

Human Drosha was cloned in 2000, when it was identified as a nuclear dsRNA ribonuclease involved in the processing of is_associated_with::ribosomal RNA precursors. The other two human enzymes that participate in the processing and activity of miRNA are the is_associated_with::Dicer and is_associated_with::Argonaute proteins.

Both Drosha and Pasha are localized to the is_associated_with::cell nucleus, where processing of pri-miRNA to pre-miRNA occurs. This latter molecule is then further processed by the RNase is_associated_with::Dicer into mature miRNAs in the cell is_associated_with::cytoplasm. Both Drosha and Dicer also participate in the DNA damage response.

Clinical significance
Drosha and other miRNA processing enzymes may be important in cancer prognosis. Both Drosha and Dicer can function as is_associated_with::master regulators of miRNA processing and have been observed to be down-regulated in some types of is_associated_with::breast cancer. However, the nature of the association between microRNA processing and is_associated_with::tumorigenesis is unclear.