Dicer
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Location (UCSC) | Chr 14: 95.09 – 95.16 Mb | Chr 12: 104.65 – 104.72 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an
Discovery
Dicer was given its name in 2001 by Stony Brook PhD student Emily Bernstein while conducting research in Gregory Hannon's lab at Cold Spring Harbor Laboratory. Bernstein sought to discover the enzyme responsible for generating small RNA fragments from double-stranded RNA. Dicer's ability to generate around 22 nucleotide RNA fragments was discovered by separating it from the RISC enzyme complex after initiating the RNAi pathway with dsRNA transfection. This experiment showed that RISC was not responsible for generating the observable small nucleotide fragments. Subsequent experiments testing RNase III family enzymes abilities to create RNA fragments narrowed the search to Drosophila CG4792, now named Dicer.[5]
Dicer
In terms of crystal structure, the first Dicer to be explored was that from the
Functional domains
Human dicer (also known as hsDicer or
Current research suggests the PAZ domain is capable of binding the 2 nucleotide 3' overhang of dsRNA while the RNaseIII catalytic domains form a pseudo-dimer around the dsRNA to initiate cleavage of the strands. This results in a functional shortening of the dsRNA strand. The distance between the PAZ and RNaseIII domains is determined by the angle of the connector helix and influences the length of the micro RNA product.
Role in RNA interference
Micro RNA
Small Interfering RNA
Disease
Macular degeneration
Age related
Cancer
Altered
Dicer is also involved in
Other conditions
Multinodular
Viral pathogenesis
Infection by
In insects
In Drosophila, Dicer-1 generates microRNAs (miRNAs) by processing pre-miRNA, Dicer-2 is responsible for producing small interfering RNAs (siRNAs) from long double-stranded RNA (dsRNA).
Diagnostic and therapeutic applications
Dicer can be used to identify whether
The siRNA was shown to be delivered in two ways in mammalian species such as mice. One way would be to directly inject into the system, which would not require Dicer function. Another way would be to introduce it by plasmids that encode for short hairpin RNA, which are cleaved by Dicer into siRNA.[29]
One of the advantages of using Dicer to produce siRNA therapeutically would be the specificity and diversity of targets it can affect compared to what is currently being used such as
Dicer-like proteins
Plant genomes encode for dicer-like proteins with similar functions and protein domains as animal and insect dicer. For example, in the model organism
Rice and grapes also produce DCLs as the dicer mechanism is a common defense strategy of many organisms. Rice has evolved other functions for the five DCLs it produces and they play a more important role in function and development than in Arabidopsis. Additionally, expression patterns differ among the different plant cell types of rice while expression in Arabidopsis is more
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000100697 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041415 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 4371481.
- PMID 18268840.
- PMID 20085706.
- ^ PMID 19836333.
- ^ S2CID 23785494.
- ^ "Entrez Gene: DICER1 Dicer1, Dcr-1 homolog (Drosophila)".
- PMID 10786632.
- S2CID 14495726.
- ^ PMID 21419681.
- S2CID 9091863.
- ^ PMID 20179193.
- PMID 15811921.
- ISBN 978-0-8053-9592-1.
- PMID 12902540.
- PMID 21412326.
- PMID 22541070.
- PMID 23222681.
- PMID 17071602.
- ^ Rivera B, Nadaf J, Fahiminiya S, Apellaniz-Ruiz M, Saskin A, Chong AS, Sharma S, Wagener R, Revil T, Condello V, Harra Z, Hamel N, Sabbaghian N, Muchantef K, Thomas C, de Kock L, Hébert-Blouin MN, Bassenden AV, Rabenstein H, Mete O, Paschke R, Pusztaszeri MP, Paulus W, Berghuis A, Ragoussis J, Nikiforov YE, Siebert R, Albrecht S, Turcotte R, Hasselblatt M, Fabian MR, Foulkes WD (2019) DGCR8 microprocessor defect characterizes familial multinodular goiter with schwannomatosis. J Clin Invest
- PMID 16563388.
- PMID 21419681.
- ^ "Mosquito-borne Diseases". National Center for Infections Disease, Center for Disease Control and Prevention. Archived from the original on 31 January 2014. Retrieved 22 April 2014.
- PMID 24732439.
- PMID 18818708.
- ^ "Gene silencing by RNA interference is being used routinely to study gene function in cultured mammalian cells". Life Technologies. Retrieved 23 April 2014.
- PMID 15520458.
- PMID 19536157.
- S2CID 28801338.