In eukaryotes, small RNA molecules engage in sequence-specific interactions to inhibit gene expression by RNA silencing. This process fulfils fundamental regulatory roles, as well as antiviral ...functions, through the activities of microRNAs and small interfering RNAs. As a counter-defence mechanism, viruses have evolved various anti-silencing strategies that are being progressively unravelled. These studies have not only highlighted our basic understanding of host-parasite interactions, but also provide key insights into the diversity, regulation and evolution of RNA-silencing pathways.
In eukaryotic RNA silencing, RNase-III classes of enzymes in the Dicer family process double-stranded RNA of cellular or exogenous origin into small-RNA (sRNA) molecules. sRNAs are then loaded into ...effector proteins known as ARGONAUTEs (AGOs), which, as part of RNA-induced silencing complexes, target complementary RNA or DNA for silencing. Plants have evolved a large variety of pathways over the Dicer-AGO consortium, which most likely underpins part of their phenotypic plasticity. Dicer-like proteins produce all known classes of plant silencing sRNAs, which are invariably stabilized via 2'-O-methylation mediated by HUA ENHANCER 1 (HEN1), potentially amplified by the action of several RNA-dependent RNA polymerases, and function through a variety of AGO proteins. Here, we review the known characteristics and biochemical properties of the core silencing factors found in the model plant Arabidopsis thaliana. We also describe how interactions between these core factors and more specialized proteins allow the production of a plethora of silencing sRNAs involved in a large array of biological functions. We emphasize in particular the biogenesis and activities of silencing sRNAs of endogenous origin.
A multitude of small RNAs (sRNAs, 18-25 nt in length) accumulate in plant tissues. Although heterogeneous in size, sequence, genomic distribution, biogenesis, and action, most of these molecules ...mediate repressive gene regulation through RNA silencing. Besides their roles in developmental patterning and maintenance of genome integrity, sRNAs are also integral components of plant responses to adverse environmental conditions, including biotic stress. Until recently, antiviral RNA silencing was considered a paradigm of the interactions linking RNA silencing to pathogens: Virus-derived sRNAs silence viral gene expression and, accordingly, viruses produce suppressor proteins that target the silencing mechanism. However, increasing evidence shows that endogenous, rather than pathogen-derived, sRNAs also have broad functions in regulating plant responses to various microbes. In turn, microbes have evolved ways to inhibit, avoid, or usurp cellular silencing pathways, thereby prompting the deployment of counter-defensive measures by plants, a compelling illustration of the never-ending molecular arms race between hosts and parasites.
In plants and several other organisms, the effects of RNA silencing can be amplified by the action of cellular RNA-DEPENDENT RNA POLYMERASES (RDRs). These enzymes were primarily studied for their ...role in antiviral defense in plants, but it is becoming increasingly apparent that they also have important endogenous functions, including the control of chromatin structure and the regulation of cellular gene expression. Recent evidence suggests that endogenous RDR activities intercept several RNA quality control pathways that normally prevent or restrain widespread amplification of silencing, which is likely to be detrimental. Plants appear, however, to have evolved sophisticated measures to tolerate or exploit amplified silencing under specific biological circumstances.
In plants and in some animals, the effects of post-transcriptional RNA silencing can extend beyond its sites of initiation, owing to the movement of signal molecules. Although the mechanisms and ...channels involved are different, plant and animal silencing signals must have RNA components that account for the nucleotide sequence-specificity of their effects. Studies carried out in plants and
Caenorhabditis elegans have revealed that non-cell autonomous silencing is operated through specialized, remarkably sophisticated pathways and serves important biological functions, including antiviral immunity and, perhaps, developmental patterning. Recent intriguing observations suggest that systemic RNA silencing pathways may also exist in higher vertebrates.
RNA silencing is a pan-eukaryotic, sequence-specific gene regulation mechanism with recognized roles in development and maintenance of genome integrity. In plants, this mechanism also operates as a ...major antiviral defense system whereby 21–24
nt-long RNAs derived from the pathogen's genomes guide post-transcriptional silencing (PTGS) of viral transcripts. Recent evidence suggests that PTGS involving small RNAs of cellular, rather than pathogenous origin, might additionally have broad implications in potentiating basal defense and race-specific resistance to microbes in plants. These studies simultaneously unravel a staggering degree of complexity and flexibility in endogenous RNA silencing pathways, a likely reflection of the plants’ faculty to adapt to their environment.
Transient populations of cis- and trans-acting small RNAs have recently emerged as key regulators of extensive epigenetic changes taking place during periconception, which encompasses gametogenesis, ...fertilization, and early zygotic development. These small RNAs are not only important to maintain genome integrity in the gametes and zygote, but they also actively contribute to assessing the compatibility of parental genomes at fertilization and to promoting long-term memory of the zygotic epigenetic landscape by affecting chromatin. Striking parallels exist in the biogenesis and modus operandi of these molecules among diverse taxa, unraveling universal themes of small-RNA-mediated epigenetic reprogramming during sexual reproduction.
► RNA silencing moves in plants from cell-to-cell and over long distances. ► Short interfering (si)RNAs, not longer precursors, are the nucleic acid involved. ► siRNAs direct long-distance ...post-transcriptional and chromatin-based silencing. ► All classes of endogenous siRNAs have the potential to move in Arabidopsis. ► Epiallelism and trans-generational memory may arise from siRNA mobility.
In plants, once triggered within a single-cell type, transgene-mediated RNA-silencing can move from cell-to-cell and over long distances through the vasculature to alter gene expression in tissues remote form the primary sites of its initiation. Although, transgenic approaches have been instrumental to genetically decipher the components and channels required for mobile silencing, the possible existence and biological significance of comparable endogenous mobile silencing pathways has remained an open question. Here, we summarize the results from recent studies that shed light on the molecular nature of the nucleic acids involved and on existing endogenous mechanisms that allow long-distance gene regulation and epigenetic modifications. We further elaborate on these and other results to propose a unified view of various non-cell autonomous RNA silencing processes that appear to differ in their genetic requirement and modes of perpetuation in plants.
Widespread Translational Inhibition by Plant miRNAs and siRNAs Brodersen, Peter; Sakvarelidze-Achard, Lali; Bruun-Rasmussen, Marianne ...
Science (American Association for the Advancement of Science),
05/2008, Letnik:
320, Številka:
5880
Journal Article
Recenzirano
Odprti dostop
High complementarity between plant microRNAs (miRNAs) and their messenger RNA targets is thought to cause silencing, prevalently by endonucleolytic cleavage. We have isolated Arabidopsis mutants ...defective in miRNA action. Their analysis provides evidence that plant miRNA-guided silencing has a widespread translational inhibitory component that is genetically separable from endonucleolytic cleavage. We further show that the same is true of silencing mediated by small interfering RNA (siRNA) populations. Translational repression is effected in part by the ARGONAUTE proteins AGO1 and AGO10. It also requires the activity of the microtubule-severing enzyme katanin, implicating cytoskeleton dynamics in miRNA action, as recently suggested from animal studies. Also as in animals, the decapping component VARICOSE (VCS)/Ge-1 is required for translational repression by miRNAs, which suggests that the underlying mechanisms in the two kingdoms are related.
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