Human Drosha was cloned in 2000, when it was identified as a nuclear dsRNA ribonuclease involved in the processing of ribosomal RNA precursors. The other two human enzymes that participate in the processing and activity of miRNA are the Dicer and Argonaute proteins.
Both Drosha and DGCR8 are localized to the cell nucleus, where processing of pri-miRNA to pre-miRNA occurs. This latter molecule is then further processed by the RNase Dicer into mature miRNAs in the cell cytoplasm. There also exists an isoform of Drosha that does not contain a nuclear localization signal, which results in the generation of c-Drosha. This variant has been shown to localize to the cell cytoplasm rather than the nucleus, but the effects on pri-miRNA processing are yet unclear.
Drosha and other miRNA processing enzymes may be important in cancer prognosis. Both Drosha and Dicer can function as master regulators of miRNA processing and have been observed to be down-regulated in some types of breast cancer. The alternative splicing patterns of Drosha in The Cancer Genome Atlas have also indicated that c-drosha appears to be enriched in various types of breast cancer, colon cancer, and esophagus cancer. However, the exact nature of the association between microRNA processing and tumorigenesis is unclear, but its function can be effectively examined by siRNA knockdown based on an independent validation.
^Wu H, Xu H, Miraglia LJ, Crooke ST (November 2000). "Human RNase III is a 160-kDa protein involved in preribosomal RNA processing". The Journal of Biological Chemistry. 275 (47): 36957–65. doi:10.1074/jbc.M005494200. PMID10948199.
^ abcLee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim VN (September 2003). "The nuclear RNase III Drosha initiates microRNA processing". Nature. 425 (6956): 415–9. doi:10.1038/nature01957. PMID14508493.
^Denli AM, Tops BB, Plasterk RH, Ketting RF, Hannon GJ (November 2004). "Processing of primary microRNAs by the Microprocessor complex". Nature. 432 (7014): 231–5. doi:10.1038/nature03049. PMID15531879.
^Han J, Lee Y, Yeom KH, Nam JW, Heo I, Rhee JK, Sohn SY, Cho Y, Zhang BT, Kim VN (June 2006). "Molecular basis for the recognition of primary microRNAs by the Drosha-DGCR8 complex". Cell. 125 (5): 887–901. doi:10.1016/j.cell.2006.03.043. PMID16751099.
Gunther M, Laithier M, Brison O (July 2000). "A set of proteins interacting with transcription factor Sp1 identified in a two-hybrid screening". Molecular and Cellular Biochemistry. 210 (1–2): 131–42. doi:10.1023/A:1007177623283. PMID10976766.
Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Rådmark O, Kim S, Kim VN (September 2003). "The nuclear RNase III Drosha initiates microRNA processing". Nature. 425 (6956): 415–9. doi:10.1038/nature01957. PMID14508493.
Gregory RI, Yan KP, Amuthan G, Chendrimada T, Doratotaj B, Cooch N, Shiekhattar R (November 2004). "The Microprocessor complex mediates the genesis of microRNAs". Nature. 432 (7014): 235–40. doi:10.1038/nature03120. PMID15531877.
Landthaler M, Yalcin A, Tuschl T (December 2004). "The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis". Current Biology. 14 (23): 2162–7. doi:10.1016/j.cub.2004.11.001. PMID15589161.
Zeng Y, Cullen BR (July 2005). "Efficient processing of primary microRNA hairpins by Drosha requires flanking nonstructured RNA sequences". The Journal of Biological Chemistry. 280 (30): 27595–603. doi:10.1074/jbc.M504714200. PMID15932881.
Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID17081983.
Sugito N, Ishiguro H, Kuwabara Y, Kimura M, Mitsui A, Kurehara H, Ando T, Mori R, Takashima N, Ogawa R, Fujii Y (December 2006). "RNASEN regulates cell proliferation and affects survival in esophageal cancer patients". Clinical Cancer Research. 12 (24): 7322–8. doi:10.1158/1078-0432.CCR-06-0515. PMID17121874.