Genetic Insight into the Domain Structure and Functions of Dicer-Type Ribonucleases

Abstract

Ribonuclease Dicer belongs to the family of RNase III endoribonucleases, the enzymes that specifically hydrolyze phosphodiester bonds found in double-stranded regions of RNAs. Dicer enzymes are mostly known for their essential role in the biogenesis of small regulatory RNAs. A typical Dicer-type RNase consists of a helicase domain, a domain of unknown function (DUF283), a PAZ (Piwi-Argonaute-Zwille) domain, two RNase III domains, and a double-stranded RNA binding domain; however, the domain composition of Dicers varies among species. Dicer and its homologues developed only in eukaryotes; nevertheless, the two enzymatic domains of Dicer, helicase and RNase III, display high sequence similarity to their prokaryotic orthologs. Evolutionary studies indicate that a combination of the helicase and RNase III domains in a single protein is a eukaryotic signature and is supposed to be one of the critical events that triggered the consolidation of the eukaryotic RNA interference. In this review, we provide the genetic insight into the domain organization and structure of Dicer proteins found in vertebrate and invertebrate animals, plants and fungi. We also discuss, in the context of the individual domains, domain deletion variants and partner proteins, a variety of Dicers’ functions not only related to small RNA biogenesis pathways.

A Tale of Two Lobsters—Transcriptomic Analysis Reveals a Potential Gap in the RNA Interference Pathway in the Tropical Rock Lobster Panulirus ornatus

“…At the N terminus, Dicer proteins possess highly conserved helicase domains which in arthropods, assist with substrate recognition [ 31 ]. The helicase of Dicer 1 proteins is unable to interact with ATP, allowing it to bind to pre-miRNAs without enacting unwinding activity, which enables the protein to ensure it is bound to the correct substrate prior to pre-miRNA cleavage [ 32 , 33 ]. Dicer 2 helicase inversely uses ATP to cleave long dsRNA into siRNAs [ 34 ].…”

“…The domain of unknown function 283 (DUF283)/Dicer dimerization domain is positioned next to the helicase domains, and shows strong similarity to known dsRNA binding domains [ 35 ]. It is believed to facilitate binding with Dicer partners, and potentially assist in RNA remodeling and base pairing, though its function is largely uncharacterised [ 33 , 36 ]. The most important dicer domains are the PAZ and RNAse III domains, which act as the core of the protein and are largely responsible for the primary dicer functions of dsRNA binding and cleavage [ 33 , 37 ].…”

“…It is believed to facilitate binding with Dicer partners, and potentially assist in RNA remodeling and base pairing, though its function is largely uncharacterised [ 33 , 36 ]. The most important dicer domains are the PAZ and RNAse III domains, which act as the core of the protein and are largely responsible for the primary dicer functions of dsRNA binding and cleavage [ 33 , 37 ]. The PAZ domain contains 3′ and 5′ binding pockets which anchor in the dsRNA substrate and separate it from the RNAse III domains forming a ‘platform domain’ which structurally, leads to the generation of small ~22 nt siRNAs [ 38 , 39 , 40 ].…”

“…The PAZ domain contains 3′ and 5′ binding pockets which anchor in the dsRNA substrate and separate it from the RNAse III domains forming a ‘platform domain’ which structurally, leads to the generation of small ~22 nt siRNAs [ 38 , 39 , 40 ]. The RNAse III domains cleave each RNA strand leading to hydrolysis of the phosphodiester bond and generating 2–3nt overhangs with a 5′ phosphate and 3′ hydroxyl group at the cleavage site which is necessary for efficient silencing downstream in the RNAi pathway [ 33 , 38 , 41 ]. The dsRNA binding domain (dsRBD) at the C terminus was initially believed to have an auxiliary role in Dicer function but has since been shown to be important in broad recognition of dsRNA and for localisation of Dicer to the nucleus [ 42 , 43 ].…”

The Significance of the DUF283 Domain for the Activity of Human Ribonuclease Dicer

“…Extensive studies have deciphered the roles of the Dicer domains in binding and processing of its canonical substrates, i.e., single-stranded hairpin precursors of miRNAs (pre-miRNAs) and dsRNAs. The helicase domain through selective interactions with the apical loop of pre-miRNAs can discriminate between substrates [15,16]. The DUF283 domain can bind single-stranded nucleic acids in vitro [17]; thus, it is possible that this domain may be involved in interactions with the apical loop of pre-miRNA hairpins as well [18].…”