Dicer is a specialized nuclease that produces RNA molecules of specific lengths for use in gene silencing pathways. Dicer relies on the correct measurement of RNA target duplexes to generate products of specific lengths. It is thought that Dicer uses its multidomain architecture to calibrate RNA product length. However, this measurement model is derived from structural information from a protozoan Dicer, and does not account for the helicase domain present in higher organisms. The Caenorhabditis elegans Dicer-related helicase 3 (DRH-3) is an ortholog of the Dicer and RIG-I family of double-strand RNA activated ATPases essential for secondary siRNA production. We find that DRH-3 specifies 22 bp RNAs by dimerization of the helicase domain, a process mediated by ATPase activity and the N-terminal domain. This mechanism for RNA length discrimination by a Dicer family protein suggests an alternative model for RNA length measurement by Dicer, with implications for recognition of siRNA and miRNA targets.
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http://dx.doi.org/10.1093/nar/gkt1383 | DOI Listing |
Nat Commun
July 2024
Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, The USTC RNA Institute, Ministry of Education Key Laboratory for Membraneless Organelles & Cellular Dynamics, Hefei National Research Center for Physical Sciences at the Microscale, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Life Sciences, Division of Life Sciences and Medicine, Biomedical Sciences and Health Laboratory of Anhui Province, University of Science and Technology of China, Hefei, Anhui, 230027, China.
Germ granules are biomolecular condensates present in most animal germ cells. One function of germ granules is to help maintain germ cell totipotency by organizing mRNA regulatory machinery, including small RNA-based gene regulatory pathways. The C.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2023
Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089.
Coordination of cellular responses to stress is essential for health across the lifespan. The transcription factor SKN-1 is an essential homeostat that mediates survival in stress-inducing environments and cellular dysfunction, but constitutive activation of SKN-1 drives premature aging thus revealing the importance of turning off cytoprotective pathways. Here, we identify how SKN-1 activation in two ciliated ASI neurons in results in an increase in organismal transcriptional capacity that drives pleiotropic outcomes in peripheral tissues.
View Article and Find Full Text PDFUnlabelled: Coordination of cellular responses to stress are essential for health across the lifespan. The transcription factor SKN-1 is an essential homeostat that mediates survival in stress-inducing environments and cellular dysfunction, but constitutive activation of SKN-1 drives premature aging thus revealing the importance of turning off cytoprotective pathways. Here we identify how SKN-1 activation in two ciliated ASI neurons in results in an increase in organismal transcriptional capacity that drives pleiotropic outcomes in peripheral tissues.
View Article and Find Full Text PDFNucleic Acids Res
September 2021
Lee Kong Chian School of Medicine, Nanyang Technological University, EMB 03-07, 59 Nanyang Drive 636921, Singapore.
DRH-3 is critically involved in germline development and RNA interference (RNAi) facilitated chromosome segregation via the 22G-siRNA pathway in Caenorhabditis elegans. DRH-3 has similar domain architecture to RIG-I-like receptors (RLRs) and belongs to the RIG-I-like RNA helicase family. The molecular understanding of DRH-3 and its function in endogenous RNAi pathways remains elusive.
View Article and Find Full Text PDFGenes (Basel)
July 2020
Molecular Genetics Laboratory, Department of Applied Chemistry and Life Science, Toyohashi University of Technology, Toyohashi, Aichi 441-8580, Japan.
The Dicer-related helicases (DRHs) are members of a helicase subfamily, and mammalian DRHs such as retinoic acid-inducible gene-I (RIG-I), are involved in antiviral immunity. DRH-1 and DRH-3 play crucial roles in antiviral function and chromosome segregation, respectively. Although intrinsic double-stranded RNA-dependent ATP-hydrolyzing activity has been observed in the recombinant DRH-3 protein prepared from , there are no reports of biochemical studies of the nematode RIG-I homolog DRH-1.
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