Drosha
Encyclopedia
Drosha is a Class 2 RNase III
enzyme
responsible for initiating the processing of microRNA (miRNA), or short RNA
molecules naturally expressed
by the cell
that regulate a wide variety of other genes by interacting with the RNA-induced silencing complex
(RISC) to induce cleavage of complementary
messenger RNA
(mRNA) as part of the RNAi
pathway. A microRNA molecule is synthesized as a long RNA primary transcript
known as a pri-miRNA, which is cleaved by Drosha to produce a characteristic stem-loop
structure of about 70 base pair
s long, known as a pre-miRNA. Drosha exists as part of a protein complex
called the Microprocessor complex, which also contains the double-stranded RNA binding protein Pasha
(also called DGCR8)., which 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 ribosomal RNA precursors. Drosha was the first human RNase III enzyme identified and cloned. The other two human enzymes that participate in the processing and activity of miRNA are the Dicer
and Argonaute
proteins.
Both Drosha and Pasha 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
.
Drosha and other miRNA processing enzymes may be important in cancer prognosis.
RNase III
RNase III enzymes specifically bind to and cleave double-stranded RNA . There are three subdivisions, known as Class 1, 2, and 3.Prokaryotic ribonuclease III is an enzyme that digests double-stranded RNA. It is involved in the processing of ribosomal RNA precursors and of some mRNAs.* Class 1...
enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
responsible for initiating the processing of microRNA (miRNA), or short RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
molecules naturally expressed
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
by the cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
that regulate a wide variety of other genes by interacting with the RNA-induced silencing complex
RNA-induced silencing complex
RNA-Induced Silencing Complex, or RISC, is a multiprotein complex that incorporates one strand of a small interfering RNA or micro RNA . RISC uses the siRNA or miRNA as a template for recognizing complementary mRNA. When it finds a complementary strand, it activates RNase and cleaves the RNA...
(RISC) to induce cleavage of complementary
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
(mRNA) as part of the RNAi
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...
pathway. A microRNA molecule is synthesized as a long RNA primary transcript
Primary transcript
A primary transcript is an RNA molecule that has not yet undergone any modification after its synthesis. For example, a precursor messenger RNA is a primary transcript that becomes a messenger RNA after processing, and a primary microRNA precursor becomes a microRNA after processing....
known as a pri-miRNA, which is cleaved by Drosha to produce a characteristic stem-loop
Stem-loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded DNA or, more commonly, in RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions,...
structure of about 70 base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...
s long, known as a pre-miRNA. Drosha exists as part of a protein complex
Protein complex
A multiprotein complex is a group of two or more associated polypeptide chains. If the different polypeptide chains contain different protein domain, the resulting multiprotein complex can have multiple catalytic functions...
called the Microprocessor complex, which also contains the double-stranded RNA binding protein Pasha
Pasha (protein)
Pasha , also known as DGCR8 in vertebrates organisms, is a protein localized to the cell nucleus that is required for microRNA processing. It binds to Drosha, an RNase III enzyme, to form the Microprocessor complex that cleaves a primary transcript known as pri-miRNA to a characteristic stem-loop...
(also called DGCR8)., which 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 ribosomal RNA precursors. Drosha was the first human RNase III enzyme identified and cloned. The other two human enzymes that participate in the processing and activity of miRNA are the Dicer
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...
and Argonaute
Argonaute
Argonaute proteins are the catalytic components of the RNA-induced silencing complex , the protein complex responsible for the gene silencing phenomenon known as RNA interference . Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs , small interfering RNAs and...
proteins.
Both Drosha and Pasha are localized to the cell nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, where processing of pri-miRNA to pre-miRNA occurs. This latter molecule is then further processed by the RNase Dicer
Dicer
Dicer is an endoribonuclease in the RNase III family that cleaves double-stranded RNA and pre-microRNA into short double-stranded RNA fragments called small interfering RNA about 20-25 nucleotides long, usually with a two-base overhang on the 3' end...
into mature miRNAs in the cell cytoplasm
Cytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
.
Drosha and other miRNA processing enzymes may be important in cancer prognosis.