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A recently characterized RNA modification is NAD+-modified RNAs (NAD-RNAs). Various enzymes decap NAD-RNAs, and Wang and Yu et al. now describe another, namely Toll/interleukin-1 receptor (TIR) domain-containing proteins of bacteria and Archaea. TIR decapping products are a specific variant of cyclic ADP ribose (ADPR)-RNAs (v-cADPR-RNAs), opening a new window to the NAD-RNA world. [ABSTRACT FROM AUTHOR]

RNA modifications immensely expand the diversity of the transcriptome, thereby influencing the function, localization, and stability of RNA. One prominent example of an RNA modification is the eukaryotic cap located at the 5′ terminus of mRNAs. Interestingly, the redox cofactor NAD can be incorporated into RNA by RNA polymerase in vitro. The existence of NAD-modified RNAs in vivo was confirmed using liquid chromatography and mass spectrometry (LC-MS). In the past few years novel technologies and methods have characterized NAD as a cap-like RNA structure and enabled the investigation of NAD-capped RNAs (NAD-RNAs) in a physiological context. We highlight the identification of NAD-RNAs as well as the regulation and functions of this epitranscriptomic mark in all domains of life. RNA 5′-ends can be decorated by the ubiquitous redox cofactor NAD in all domains of life. NAD-capped RNAs are usually synthesized by transcription initiation using NAD as a substrate by RNA polymerase; NAD-caps are removed by decapping enzymes in pro- and eukaryotes, and by deNADding enzymes in eukaryotes only. The NAD-cap protects RNA against nucleases in prokaryotes; by contrast, the cap marks eukaryotic RNA molecules for decay. The presence of NAD-RNAs varies depending on the metabolic state of the organism. Functions of NAD-RNAs beyond RNA stability modulation remain poorly understood, for instance their potential to be translated in vivo. In addition, NAD-RNAs are described as novel substrates for ADP-ribosyltransferases that covalently link proteins and RNAs (RNAylation). [ABSTRACT FROM AUTHOR]

Animal development is dictated by the selective and timely decay of mRNAs in developmental transitions, but the impact of mRNA decapping scaffold proteins in development is unclear. This study unveils the roles and interactions of the DCAP-2 decapping scaffolds EDC-3 and EDC-4 in the embryonic development of C. elegans. EDC-3 facilitates the timely removal of specific embryonic mRNAs, including cgh-1 , car-1 , and ifet-1 by reducing their expression and preventing excessive accumulation of DCAP-2 condensates in somatic cells. We further uncover a role for EDC-3 in defining the boundaries between P bodies, germ granules, and stress granules. Finally, we show that EDC-4 counteracts EDC-3 and engenders the assembly of DCAP-2 with the GID (CTLH) complex, a ubiquitin ligase involved in maternal-to-zygotic transition (MZT). Our findings support a model where multiple RNA decay mechanisms temporally clear maternal and zygotic mRNAs throughout embryonic development. [Display omitted] • EDC-3 restricts and EDC-4 promotes DCAP-2/P body condensate assembly • EDC-3 promotes clearance of decapping scaffold mRNAs in the germline and soma • EDC-3 prevents aberrant scaffolding of condensate proteins on DCAP-2 • EDC-4 facilitates DCAP-2 interaction with the GID (CTLH) complex The timely decay of mRNAs is essential for the embryonic development of all metazoans. Vidya et al. detail how two decapping scaffold proteins (EDC-3 and EDC-4) distinctly regulate the localization and interactions of DCAP-2, an enzyme that irreversibly catalyzes mRNA decay, into cytoplasmic condensates throughout C. elegans embryonic development. [ABSTRACT FROM AUTHOR]

RNA decay plays a crucial role in post-transcriptional regulation of gene expression. Work conducted over the last decades has defined the major mRNA decay pathways, as well as enzymes and their cofactors responsible for these processes. In contrast, our knowledge of the mechanisms of degradation of non-protein coding RNA species is more fragmentary. This review is focused on the cytoplasmic pathways of mRNA and ncRNA degradation in eukaryotes. The major 3′ to 5′ and 5′ to 3′ mRNA decay pathways are described with emphasis on the mechanisms of their activation by the deprotection of RNA ends. More recently discovered 3′-end modifications such as uridylation, and their relevance to cytoplasmic mRNA decay in various model organisms, are also discussed. Finally, we provide up-to-date findings concerning various pathways of non-coding RNA decay in the cytoplasm. [ABSTRACT FROM AUTHOR]

Abstract: Atomic structure models of semiconductor surfaces consider usually ideal models based on density functional theory calculations. In reality, however, semiconductor surfaces exhibit a variety of defects which deviate from this ideal surface structure. Depending on their specific nature and amount, these defects can contribute significantly to the total energy of the surface. Furthermore, the electronic properties and consequently their specific reactivity towards adsorption processes can be modified significantly due to the existence of surface defects. Here, we present an analysis of different kinds of defects at the GaAs(001)-c(4×4) surface reconstruction. The surfaces were prepared by thermal decapping of GaAs(001) epilayers grown by molecular beam epitaxy and capped by an amorphous As cap. High resolution measurements with scanning tunneling microscopy were performed at room temperature and allowed the identification and atomic analysis of several different kinds of surface defects. Apart from other defects we found indications that approximately 3% of the surface dimers are incomplete, consisting only of one As atom instead of two. [Copyright &y& Elsevier]

Abstract: Messenger RNA degradation is a fundamental cellular process that plays a critical role in regulating gene expression by controlling both the quality and the abundance of mRNAs in cells. Naturally, viruses must successfully interface with the robust cellular RNA degradation machinery to achieve an optimal balance between viral and cellular gene expression and establish a productive infection in the host. In the past several years, studies have discovered many elegant strategies that viruses have evolved to circumvent the cellular RNA degradation machinery, ranging from disarming the RNA decay pathways and co-opting the factors governing cellular mRNA stability to promoting host mRNA degradation that facilitates selective viral gene expression and alters the dynamics of host–pathogen interaction. This review summarizes the current knowledge of the multifaceted interaction between viruses and cellular mRNA degradation machinery to provide an insight into the regulatory mechanisms that influence gene expression in viral infections. This article is part of a Special Issue entitled: RNA Decay mechanisms. [Copyright &y& Elsevier]

Abstract: The post-transcriptional addition of non-templated nucleotides to the 3′ ends of RNA molecules can have a profound impact on their stability and biological function. Evidence accumulated over the past few decades has identified roles for polyadenylation in RNA stabilisation, degradation and, in the case of eukaryotic mRNAs, translational competence. By contrast, the biological significance of RNA 3′ modification by uridylation has only recently started to become apparent. The evolutionary origin of eukaryotic RNA terminal uridyltransferases can be traced to an ancestral poly(A) polymerase. Here we review what is currently known about the biological roles of these enzymes, the ways in which their activity is regulated and the consequences of this covalent modification for the target RNA molecule, with a focus on those instances where uridylation has been found to contribute to RNA degradation. Roles for uridylation have been identified in the turnover of mRNAs, pre-microRNAs, piwi-interacting RNAs and the products of microRNA-directed mRNA cleavage; many mature microRNAs are also modified by uridylation, though the consequences in this case are currently less well understood. In the case of piwi-interacting RNAs, modification of the 3′-terminal nucleotide by the HEN1 methyltransferase blocks uridylation and so stabilises the small RNA. The extent to which other uridylation-dependent mechanisms of RNA decay are similarly regulated awaits further investigation. This article is part of a Special Issue entitled: RNA Decay mechanisms. [Copyright &y& Elsevier]

Abstract: The regulation of mRNA degradation is critical for proper gene expression. Many major pathways for mRNA decay involve the removal of the 5′ 7-methyl guanosine (m7G) cap in the cytoplasm to allow for 5′-to-3′ exonucleolytic decay. The most well studied and conserved eukaryotic decapping enzyme is Dcp2, and its function is aided by co-factors and decapping enhancers. A subset of these factors can act to enhance the catalytic activity of Dcp2, while others might stimulate the remodeling of proteins bound to the mRNA substrate that may otherwise inhibit decapping. Structural studies have provided major insights into the mechanisms by which Dcp2 and decapping co-factors activate decapping. Additional mRNA decay factors can function by recruiting components of the decapping machinery to target mRNAs. mRNA decay factors, decapping factors, and mRNA substrates can be found in cytoplasmic foci named P bodies that are conserved in eukaryotes, though their function remains unknown. In addition to Dcp2, other decapping enzymes have been identified, which may serve to supplement the function of Dcp2 or act in independent decay or quality control pathways. This article is part of a Special Issue entitled: RNA Decay mechanisms. [Copyright &y& Elsevier]

Abstract: Luteinizing hormone receptor undergoes downregulation during preovulatory Luteinizing hormone surge through a post-transcriptional mechanism involving an RNA binding protein designated as LRBP. The present study examined the mechanism by which LRBP induces the degradation of Luteinizing hormone receptor mRNA, specifically the role of decapping of Luteinizing hormone receptor mRNA and the translocation of LRBP-bound Luteinizing hormone receptor mRNA to degradative machinery. Immunoprecipitation of the complex with the 5′cap structure antibody followed by real time PCR analysis showed progressive loss of capped Luteinizing hormone receptor mRNA during downregulation suggesting that Luteinizing hormone receptor mRNA undergoes decapping prior to degradation. RNA immunoprecipitation analysis confirmed dissociation of eukaryotic initiation factor 4E from the cap structure, a step required for decapping. Furthermore, RNA immunoprecipitation analysis using antibody against the p body marker protein, DCP1A showed that Luteinizing hormone receptor mRNA was associated with the p bodies, the cytoplasmic foci that contain RNA degradative enzymes and decapping complex. Immunohistochemical studies using antibodies against LRBP and DCP1A followed by confocal analysis showed colocalization of LRBP with DCP1A during downregulation. This was further confirmed by co-immunoprecipitation of LRBP with DCP1A. The association of LRBP and Luteinizing hormone receptor mRNA in the p bodies during downregulation was further confirmed by examining the association of a second p body component, rck/p54, using immunoprecipitation and RNA immunoprecipitation respectively. These data suggest that the association of LRBP with Luteinizing hormone receptor mRNA results in the translocation of the messenger ribonucleoprotein complex to the p bodies leading to decapping and degradation. [Copyright &y& Elsevier]

Abstract: Messenger RNA degradation is an important point of control for gene expression. Genome-wide studies on mRNA stability have demonstrated its importance in adaptation and stress response. Most of the key players in mRNA decay appear to have been identified. The study of these proteins brings insight into the mechanism of general and specific targeting of transcripts for degradation. Recruitment and assembly of mRNP complexes enhance and bring specificity to mRNA decay. mRNP complexes can form larger structures that have been found to be ubiquitous in nature. Discovery of P-Bodies, an archetype of this sort of aggregates, has generated interest in the question of where mRNA degrades. This is currently an open question under extensive investigation. This review will discuss in detail the recent developments in the regulation of mRNA decay focusing on yeast as a model system. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing. [Copyright &y& Elsevier]

Abstract: In yeast, the activators of mRNA decapping, Pat1, Lsm1 and Dhh1, accumulate in processing bodies (P bodies) together with other proteins of the 5′-3′-deadenylation-dependent mRNA decay pathway. The Pat1 protein is of particular interest because it functions in the opposing processes of mRNA translation and mRNA degradation, thus suggesting an important regulatory role. In contrast to other components of this mRNA decay pathway, the human homolog of the yeast Pat1 protein was unknown. Here we describe the identification of two human PAT1 genes and show that one of them, PATL1, codes for an ORF with similar features as the yeast PAT1. As expected for a protein with a fundamental role in translation control, PATL1 mRNA was ubiquitously expressed in all human tissues as were the mRNAs of LSM1 and RCK, the human homologs of yeast LSM1 and DHH1, respectively. Furthermore, fluorescence-tagged PatL1 protein accumulated in distinct foci that correspond to P bodies, as they co-localized with the P body components Lsm1, Rck/p54 and the decapping enzyme Dcp1. In addition, as for its yeast counterpart, PatL1 expression was required for P body formation. Taken together, these data emphasize the conservation of important P body components from yeast to human cells. [Copyright &y& Elsevier]

Abstract: Four novel 5′ mRNA cap analogs have been synthesized with one of the pyrophosphate bridge oxygen atoms of the triphosphate linkage replaced with a methylene group. The analogs were prepared via reaction of nucleoside phosphor/phosphon-1-imidazolidates with nucleoside phosphate/phosphonate in the presence of ZnCl2. Three of the new cap analogs are completely resistant to degradation by human DcpS, the enzyme responsible for hydrolysis of free cap resulting from 3′ to 5′ cellular mRNA decay. One of the new analogs has very high affinity for binding to human DcpS. Two of these analogs are Anti Reverse Cap Analogs which ensures that they are incorporated into mRNA chains exclusively in the correct orientation. These new cap analogs should be useful in a variety of biochemical studies, in the analysis of the cellular function of decapping enzymes, and as a basis for further development of modified cap analogs as potential anti-cancer and anti-parasite drugs. [Copyright &y& Elsevier]