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      5′ and 3′ modifications controlling RNA degradation: from safeguards to executioners

      1 , 2 , 3
      Philosophical Transactions of the Royal Society B: Biological Sciences
      The Royal Society

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          Abstract

          <p class="first" id="d2659693e185">RNA degradation is a key process in the regulation of gene expression. In all organisms, RNA degradation participates in controlling coding and non-coding RNA levels in response to developmental and environmental cues. RNA degradation is also crucial for the elimination of defective RNAs. Those defective RNAs are mostly produced by ‘mistakes’ made by the RNA processing machinery during the maturation of functional transcripts from their precursors. The constant control of RNA quality prevents potential deleterious effects caused by the accumulation of aberrant non-coding transcripts or by the translation of defective messenger RNAs (mRNAs). Prokaryotic and eukaryotic organisms are also under the constant threat of attacks from pathogens, mostly viruses, and one common line of defence involves the ribonucleolytic digestion of the invader's RNA. Finally, mutations in components involved in RNA degradation are associated with numerous diseases in humans, and this together with the multiplicity of its roles illustrates the biological importance of RNA degradation. RNA degradation is mostly viewed as a default pathway: any functional RNA (including a successful pathogenic RNA) must be protected from the scavenging RNA degradation machinery. Yet, this protection must be temporary, and it will be overcome at one point because the ultimate fate of any cellular RNA is to be eliminated. This special issue focuses on modifications deposited at the 5′ or the 3′ extremities of RNA, and how these modifications control RNA stability or degradation. </p><p id="d2659693e187">This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.</p>

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          Most cited references43

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          Rethinking m6A Readers, Writers, and Erasers.

          In recent years, m6A has emerged as an abundant and dynamically regulated modification throughout the transcriptome. Recent technological advances have enabled the transcriptome-wide identification of m6A residues, which in turn has provided important insights into the biology and regulation of this pervasive regulatory mark. Also central to our current understanding of m6A are the discovery and characterization of m6A readers, writers, and erasers. Over the last few years, studies into the function of these proteins have led to important discoveries about the regulation and function of m6A. However, during this time our understanding of these proteins has also evolved considerably, sometimes leading to the reversal of early concepts regarding the reading, writing and erasing of m6A. In this review, we summarize recent advances in m6A research, and we highlight how these new findings have reshaped our understanding of how m6A is regulated in the transcriptome.
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            Methylation as a crucial step in plant microRNA biogenesis.

            Methylation on the base or the ribose is prevalent in eukaryotic ribosomal RNAs (rRNAs) and is thought to be crucial for ribosome biogenesis and function. Artificially introduced 2'-O-methyl groups in small interfering RNAs (siRNAs) can stabilize siRNAs in serum without affecting their activities in RNA interference in mammalian cells. Here, we show that plant microRNAs (miRNAs) have a naturally occurring methyl group on the ribose of the last nucleotide. Whereas methylation of rRNAs depends on guide RNAs, the methyltransferase protein HEN1 is sufficient to methylate miRNA/miRNA* duplexes. Our studies uncover a new and crucial step in plant miRNA biogenesis and have profound implications in the function of miRNAs.
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              Poly(A)-tail profiling reveals an embryonic switch in translational control

              Poly(A) tails enhance the stability and translation of most eukaryotic mRNAs, but difficulties in globally measuring poly(A)-tail lengths have impeded greater understanding of poly(A)-tail function. Here, we describe poly(A)-tail length profiling by sequencing (PAL-seq) and apply it to measure tail lengths of millions of individual RNAs isolated from yeasts, cell lines, Arabidopsis leaves, mouse liver, and zebrafish and frog embryos. Poly(A)-tail lengths were conserved between orthologous mRNAs, with mRNAs encoding ribosomal proteins and other “housekeeping” proteins tending to have shorter tails. As expected, tail lengths were coupled to translational efficiency in early zebrafish and frog embryos. However, this strong coupling diminished at gastrulation and was absent in non-embryonic samples, indicating a rapid developmental switch in the nature of translational control. This switch complements an earlier switch to zygotic transcriptional control and explains why the predominant effect of microRNA-mediated deadenylation concurrently shifts from translational repression to mRNA destabilization.
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                Author and article information

                Journal
                Philosophical Transactions of the Royal Society B: Biological Sciences
                Phil. Trans. R. Soc. B
                The Royal Society
                0962-8436
                1471-2970
                November 05 2018
                December 19 2018
                November 05 2018
                December 19 2018
                : 373
                : 1762
                : 20180160
                Affiliations
                [1 ]Institut de biologie moléculaire des plantes (IBMP), Centre national de la recherche scientifique (CNRS), Université de Strasbourg, 12 rue Zimmer, 67000 Strasbourg, France
                [2 ]Laboratory of RNA Biology and Functional Genomics, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a, 02-106 Warsaw, Poland
                [3 ]Institute of Genetics and Biotechnology, Faculty of Biology, University of Warsaw, Pawinskiego 5a, 02-106 Warsaw, Poland
                Article
                10.1098/rstb.2018.0160
                b0e25a99-178c-46f6-8a8e-0c9e1349ca69
                © 2018

                https://royalsociety.org/-/media/journals/author/Licence-to-Publish-20062019-final.pdf

                https://royalsociety.org/journals/ethics-policies/data-sharing-mining/

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