The following text describes a protein:
Function:
[Isoform PA]: Double-stranded RNA-binding protein which can function in gene silencing by acting with Dcr-1 to enhance its ATP-independent processing of a specific subset of precursor micro-RNAs (pre-miRNAs) to mature miRNAs. Some reports found it was able to enhance the efficiency of pre-miRNA processing by Dcr-1, and can shift the cleavage site of Dcr-1 altering the length of the mature miRNAs produced by Dcr-1 alone. However, in contrast to isoform PB, it is not necessary or sufficient for enhancing miRNA biogenesis, and is not required for development or female germline stem cell (GSC) maintenance. Another report also found that it decreases binding of Dcr-1 to the miRNA substrate let-7; [Isoform PB]: Double-stranded RNA-binding protein which functions in gene silencing by acting with Dcr-1 to enhance its ATP-independent processing of a specific subset of precursor micro-RNAs (pre-miRNAs) to mature miRNAs. Function is essential for development and female germline stem cell (GSC) maintenance. Functions in miRNA-mediated gene silencing by enhancing the binding affinity and specific pre-miRNA processing activity of Dcr-1, and as part of the loqs-PB-Dcr-1 complex, is involved in substrate discrimination, correctly positioning the pre-miRNA in the Dcr-1 catalytic center for cleavage, and miRNA loading into the Argonaute 1 (Ago1)-containing RNA-induced silencing complex (miRISC). Increases the binding affinity of Dcr-1 to pre-miRNAs, thereby increasing dicing efficiency and broadening the range of substrates that can be processed by the dicer. It may also confer the substrate specificity of Dcr-1 towards pre-miRNAs, as in its absence Dcr-1 displays siRNA-generating activity towards long dsRNA substrates. It can also shift the cleavage site of Dcr-1 for a small number of pre-miRNAs, changing the length of the mature miRNAs produced by Dcr-1 alone. Increases the range of pre-miRNAs that can be processed by Dcr-1, by enhancing the dicing of suboptimal hairpin substrates including ones with mismatches at the dicing site. This function may also promote the generation of novel miRNA genes as it appears to have an important role in processing evolutionarily young miRNA genes, suggesting that it may also enhance dicing of substrates that have not acquired hairpin features required for efficient miRNA processing. As newly emerged miRNAs can have deleterious or beneficial effects on fitness, this function is likely part of a regulatory system that prevents excessive emergence of active miRNA genes and thus keeps them within an optimal range. Also forms a RISC loading complex (miRLC) with Dcr-1 to mediate Ago1-loading of mature miRNAs into the RNA-induced silencing complex (miRISC). In female ovaries, required for Dcr-1 to generate the twenty-three nucleotide isomiR variant of miR-307a which is able to repress its targets Gk2 and tara; [Isoform PD]: Double-stranded RNA-binding protein which has an essential role in gene silencing (RNAi) by acting with Dcr-2 to enhance its ATP-dependent processing of a subset of endogenous (endo) and exogenous (exo) dsRNAs into short interfering RNAs (siRNAs). Functions in RNAi by increasing the initial binding affinity of Dcr-2 to certain dsRNA substrates, and in the absence of r2d2, may also function in siRNA loading into the Argonaute 2 (AGO2)-containing RNA-induced silencing complex (siRISC) and guide strand selection for target silencing by the siRISC. Promotes Dcr-2 cleavage of a subset of dsRNAs, including endo-dsRNAs derived from convergent transcription, inverted repeats and transposons. Also enables Dcr-2 to produce hairpin-derived endo-siRNAs in the presence of cellular inhibitory inorganic phosphate, likely by increasing the binding affinity of the enzyme to the hairpin dsRNAs allowing the dsRNA to displace phosphate bound to Dcr-2. According to many reports, the cleavage reaction mode of Dcr-2 changes according to the termini of the dsRNA substrate, with the enzyme displaying a preference for processing blunt termini (BLT), likely non-self dsRNAs, over dsRNAs with 2 nucleotides 3' overhanging (3'ovr) termini, which are typically the structure of endo-dsRNAs. According to many reports, interaction with Loqs-PD modifies the molecular recognition mechanisms of Dcr-2 towards sub-optimal 3'ovr dsRNA substrates and thus enables the dicer to cleave endo-dsRNA templates with diverse termini. However, according to another report, the mode of cleavage reaction is not affected by the presence or absence of loqs-PD. In the absence of r2d2, may also form an alternative RISC loading complex (siRLC) with Dcr-2 to mediate AGO2-loading of endo- and exo-siRNAs into the RNA-induced silencing complex (siRISC). Many reports suggest that loqs-PD and r2d2 function independently with dcr-2 in distinct siRNA pathways, and may even compete for binding to the enzyme. Loaded siRNAs serve as a guide to direct the siRISC to complementary RNAs to degrade them or prevent their translation. The siRLC plays an important role in the ATP-dependent asymmetry sensing of the duplex, and is therefore also responsible for the selection of the strand that ultimately acts as the guide siRNA for the siRISC. Thermodynamically asymmetric endo-siRNAs can be pre-oriented in the siRLC by the Loqs-PD and DCr-2 complex, which preferentially binds to the most thermodynamically stable strand prior to loading into the siRISC. Appears to be involved in promoting double-strand breaks (DSBs) following exposure to a low-dose/dose-rate (LDR) of ionizing radiation.
Miscellaneous:
MISCELLANEOUS: The name 'Loquacious' refers to the mutants being 'very talkative' as they display a loss of several types of gene silencing.
Subcellular Localization:
Cytoplasm. Cytoplasm, cytosol.
Domain:
RNA-binding DRBM domains 1 and 2 bind dsRNA while DRBM 3 binds Dcr-1. The RNA-binding DRBM 1 and 2 domains are able to bind dsRNA independently. The DRBM domains appears to bind to the RNA duplex and then slide along the siRNA helix to the ends of the siRNA. The DRBMs display a preference for binding to the more thermodynamically stable ends of the siRNA which is enhanced by interaction with Dcr-2. This suggests that the domains may also function to pre-orientate the guide strand prior to loading into the (AGO2)-containing RNA-induced silencing complex (siRISC). Both of the DRBM 1 and 2 domains are required for optimal Dcr-2 mediated cleavage of 3' overhanging termini (3'ovr) dsRNAs, whereas only the DRBM 3 domain appears to be necessary for Dcr-2 mediated cleavage of blunt termini (BLT) dsRNAs.
Sequence:
MDQENFHGSSLPQQLQNLHIQPQQASPNPVQTGFAPRRHYNNLVGLGNGNAVSGSPVKGAPLGQRHVKLKKEKISAQVAQLSQPGQLQLSDVGDPALAGGSGLQGGVGLMGVILPSDEALKFVSETDANGLAMKTPVSILQELLSRRGITPGYELVQIEGAIHEPTFRFRVSFKDKDTPFTAMGAGRSKKEAKHAAARALIDKLIGAQLPESPSSSAGPSVTGLTVAGSGGDGNANATGGGDASDKTVGNPIGWLQEMCMQRRWPPPSYETETEVGLPHERLFTIACSILNYREMGKGKSKKIAKRLAAHRMWMRLQETPIDSGKISDSICGELEGEPRSSENYYGELKDISVPTLTTQHSNKVSQFHKTLKNATGKKLLKLQKTCLKNNKIDYIKLLGEIATENQFEVTYVDIEEKTFSGQFQCLVQLSTLPVGVCHGSGPTAADAQRHAAQNALEYLKIMTKK