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piRNAs coordinate poly(UG) tailing to prevent aberrant and perpetual gene silencing
Curr Biol. 2021 Aug 14:S0960-9822(21)01066-6. doi: 10.1016/j.cub.2021.07.076. Online ahead of print.ABSTRACTNoncoding RNAs have emerged as mediators of transgenerational epigenetic inheritance (TEI) in a number of organisms. A robust example of such RNA-directed TEI is the inheritance of gene-silencing states following RNA interference (RNAi) in the metazoan C. elegans. During RNAi inheritance, gene silencing is transmitted by a self-perpetuating cascade of siRNA-directed poly(UG) tailing of mRNA fragments (pUGylation), followed by siRNA synthesis from poly(UG)-tailed mRNA templates (termed pUG RNA/siRNA cycling). Despite ...
Source: Current Biology - August 24, 2021 Category: Biology Authors: Aditi Shukla Roberto Perales Scott Kennedy Source Type: research

Loss of Small-RNA-Directed DNA Methylation in the Plant Cell Cycle Promotes Germline Reprogramming and Somaclonal Variation.
Abstract 5-methyl cytosine is widespread in plant genomes in both CG and non-CG contexts. During replication, hemi-methylation on parental DNA strands guides symmetric CG methylation on nascent strands, but non-CG methylation requires modified histones and small RNA guides. Here, we used immortalized Arabidopsis cell suspensions to sort replicating nuclei and determine genome-wide cytosine methylation dynamics during the plant cell cycle. We find that symmetric mCG and mCHG are selectively retained in actively dividing cells in culture, whereas mCHH is depleted. mCG becomes transiently asymmetric during S phase bu...
Source: Current Biology - November 27, 2020 Category: Biology Authors: Borges F, Donoghue MTA, LeBlanc C, Wear EE, Tanurdžić M, Berube B, Brooks A, Thompson WF, Hanley-Bowdoin L, Martienssen RA Tags: Curr Biol Source Type: research

Bub1 is not essential for the checkpoint response to unattached kinetochores in diploid human cells.
Abstract Error-free chromosome segregation during mitosis depends on a functional spindle assembly checkpoint (SAC). The SAC is a multi-component signalling system that is recruited to unattached or incorrectly attached kinetochores to catalyse the formation of a soluble inhibitor, known as the Mitotic Checkpoint Complex (MCC), which binds and inhibits the anaphase promoting complex (APC/C) [1]. We have previously proposed that two separable pathways, composed of KNL1-Bub3-Bub1 (KBB) and Rod-Zwilch-Zw10 (RZZ), recruit Mad1-Mad2 complexes to human kinetochores to activate the SAC [2]. Although Bub1 is absolutely re...
Source: Current Biology - September 10, 2018 Category: Biology Authors: Currie CE, Mora-Santos M, Smith CA, McAinsh AD, Millar JBA Tags: Curr Biol Source Type: research

NUP98 Sets the Size-Exclusion Diffusion Limit through the Ciliary Base.
Abstract The primary cilium maintains a well-regulated complement of soluble and membrane proteins, allowing it to mediate a variety of signaling pathways that are essential for development and tissue homeostasis [1-3]. Entry into the cilium is regulated at the base, where a complex containing nucleoporins, referred to as the "ciliary pore complex" (CPC), has been proposed to set a size-exclusion limit for soluble molecule diffusion into the cilium [4-6]. Here, using a fluorescence-based diffusion trap system, we demonstrate that NUP98, a component of the phenylalanine-glycine (FG) hydrogel permeability barrier at...
Source: Current Biology - April 26, 2018 Category: Biology Authors: Endicott SJ, Brueckner M Tags: Curr Biol Source Type: research

The THO Complex Non-Cell-Autonomously Represses Female Germline Specification through the TAS3-ARF3 Module.
Abstract In most sexually reproducing plants, a single somatic, sub-epidermal cell in an ovule is selected to differentiate into a megaspore mother cell, which is committed to giving rise to the female germline. However, it remains unclear how intercellular signaling among somatic cells results in only one cell in the sub-epidermal layer differentiating into the megaspore mother cell. Here we uncovered a role of the THO complex in restricting the megaspore mother cell fate to a single cell. Mutations in TEX1, HPR1, and THO6, components of the THO/TREX complex, led to the formation of multiple megaspore mother cell...
Source: Current Biology - May 24, 2017 Category: Biology Authors: Su Z, Zhao L, Zhao Y, Li S, Won S, Cai H, Wang L, Li Z, Chen P, Qin Y, Chen X Tags: Curr Biol Source Type: research

The Nrde Pathway Mediates Small-RNA-Directed Histone H3 Lysine 27 Trimethylation in Caenorhabditis elegans.
Abstract Small-RNA-mediated chromatin modifications have been widely studied in plants and S. pombe [1-3]. However, direct evidence of small-RNA-guided sequence-specific chromatin alterations is scarce in animals [4-7]. In C. elegans, the nuclear RNAi defective (Nrde) pathway functions to transport siRNA from the cytoplasm to the nucleus, modulate transcription elongation, induce histone H3 lysine 9 (H3K9) trimethylation, and mediate transgenerational inheritance of RNAi [8-17]. Here, we show that both exogenous RNAi and NRDE-bound endogenous 22G RNAs can direct sequence-specific histone H3 lysine 27 (H3K27) t...
Source: Current Biology - September 9, 2015 Category: Biology Authors: Mao H, Zhu C, Zong D, Weng C, Yang X, Huang H, Liu D, Feng X, Guang S Tags: Curr Biol Source Type: research

Ancient Endo-siRNA Pathways Reveal New Tricks.
Abstract Endogenously produced small interfering RNAs (endo-siRNAs, 18-30 nucleotides) play a key role in gene regulatory pathways, guiding Argonaute effector proteins as a part of a functional ribonucleoprotein complex called the RISC (RNA induced silencing complex) to complementarily target nucleic acid. Enabled by the advent of high throughput sequencing, there has been an explosion in the identification of endo-siRNAs in all three kingdoms of life since the discovery of the first microRNA in 1993. Concurrently, our knowledge of the variety of cellular processes in which small RNA pathways related to RNA interf...
Source: Current Biology - August 4, 2014 Category: Biology Authors: Claycomb JM Tags: Curr Biol Source Type: research

MUT-14 and SMUT-1 DEAD Box RNA Helicases Have Overlapping Roles in Germline RNAi and Endogenous siRNA Formation.
Abstract More than 2,000 C. elegans genes are targeted for RNA silencing by the mutator complex, a specialized small interfering RNA (siRNA) amplification module which is nucleated by the Q/N-rich protein MUT-16. The mutator complex localizes to Mutator foci adjacent to P granules at the nuclear periphery in germ cells [1]. Here, we show that the DEAD box RNA helicase smut-1 functions redundantly in the mutator pathway with its paralog mut-14 during RNAi. Mutations in both smut-1 and mut-14 also cause widespread loss of endogenous siRNAs. The targets of mut-14 and smut-1 largely overlap with the targets of other ...
Source: Current Biology - March 26, 2014 Category: Biology Authors: Phillips CM, Montgomery BE, Breen PC, Roovers EF, Rim YS, Ohsumi TK, Newman MA, van Wolfswinkel JC, Ketting RF, Ruvkun G, Montgomery TA Tags: Curr Biol Source Type: research

The Vasa Homolog RDE-12 Engages Target mRNA and Multiple Argonaute Proteins to Promote RNAi in C. elegans.
Abstract Argonaute (AGO) proteins are key nuclease effectors of RNAi [1]. Although purified AGOs can mediate a single round of target RNA cleavage in vitro, accessory factors are required for small interfering RNA (siRNA) loading and to achieve multiple-target turnover [2, 3]. To identify AGO cofactors, we immunoprecipitated the C. elegans AGO WAGO-1, which engages amplified small RNAs during RNAi [4]. These studies identified a robust association between WAGO-1 and a conserved Vasa ATPase-related protein RDE-12. rde-12 mutants are deficient in RNAi, including viral suppression, and fail to produce amplified sec...
Source: Current Biology - March 26, 2014 Category: Biology Authors: Shirayama M, Stanney W, Gu W, Seth M, Mello CC Tags: Curr Biol Source Type: research

The DEAD Box Helicase RDE-12 Promotes Amplification of RNAi in Cytoplasmic Foci in C. elegans.
We report that RDE-12, a conserved phenylalanine-glycine (FG) domain-containing DEAD box helicase, localizes in P granules and cytoplasmic foci that are enriched in RSD-6 but are excluded from the Mutator foci. Our results suggest that RDE-12 promotes secondary siRNA synthesis by orchestrating the recruitment of RDE-10 and RRF-1 to primary siRNA-targeted mRNA in distinct cytoplasmic compartments. PMID: 24684930 [PubMed - as supplied by publisher]
Source: Current Biology - March 26, 2014 Category: Biology Authors: Yang H, Vallandingham J, Shiu P, Li H, Hunter CP, Mak HY Tags: Curr Biol Source Type: research

A Role for Myosin II in Mammalian Mitochondrial Fission.
Abstract Mitochondria are dynamic organelles, undergoing both fission and fusion regularly in interphase cells. Mitochondrial fission is thought to be part of a quality-control mechanism whereby damaged mitochondrial components are segregated from healthy components in an individual mitochondrion, followed by mitochondrial fission and degradation of the damaged daughter mitochondrion [1]. Fission also plays a role in apoptosis [2]. Defects in mitochondrial dynamics can lead to neurodegenerative diseases such as Alzheimer's disease [3]. Mitochondrial fission requires the dynamin GTPase Drp1, which assembles in a ri...
Source: Current Biology - January 28, 2014 Category: Biology Authors: Korobova F, Gauvin TJ, Higgs HN Tags: Curr Biol Source Type: research

Vav1 as a Central Regulator of Invadopodia Assembly.
Abstract Invadopodia are protrusive structures used by tumor cells for degradation of the extracellular matrix to promote invasion [1]. Invadopodia formation and function are regulated by cytoskeletal-remodeling pathways and the oncogenic kinase Src. The guanine nucleotide exchange factor Vav1, which is an activator of Rho family GTPases, is ectopically expressed in many pancreatic cancers, where it promotes tumor cell survival and migration [2, 3]. We have now determined that Vav1 is also a potent regulator of matrix degradation by pancreatic tumor cells as depletion of Vav1 by siRNA-mediated knockdown inhibits t...
Source: Current Biology - December 11, 2013 Category: Biology Authors: Razidlo GL, Schroeder B, Chen J, Billadeau DD, McNiven MA Tags: Curr Biol Source Type: research