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Kim, Sungchul,Lee, Sanghyun,Shin, Jinwook,Kim, Youngkyun,Evnouchidou, Irini,Kim, Donghyun,Kim, Young-Kook,Kim, Young-Eui,Ahn, Jin-Hyun,Riddell, Stanley R,Stratikos, Efstratios,Kim, V Narry,Ahn, Kwangs Nature Publishing Group, a division of Macmillan P 2011 NATURE IMMUNOLOGY Vol.12 No.10
Major histocompatibility complex (MHC) class I molecules present peptides on the cell surface to CD8<SUP>+</SUP> T cells, which is critical for the killing of virus-infected or transformed cells. Precursors of MHC class I??presented peptides are trimmed to mature epitopes by the aminopeptidase ERAP1. The US2??US11 genomic region of human cytomegalovirus (HCMV) is dispensable for viral replication and encodes three microRNAs (miRNAs). We show here that HCMV miR-US4-1 specifically downregulated ERAP1 expression during viral infection. Accordingly, the trimming of HCMV-derived peptides was inhibited, which led to less susceptibility of infected cells to HCMV-specific cytotoxic T lymphocytes (CTLs). Our findings identify a previously unknown viral miRNA??based CTL-evasion mechanism that targets a key step in the MHC class I antigen-processing pathway.
PKR is activated by cellular dsRNAs during mitosis and acts as a mitotic regulator
Kim, Yoosik,Lee, Jung Hyun,Park, Jong-Eun,Cho, Jun,Yi, Hyerim,Kim, V. Narry Cold Spring Harbor Laboratory Press 2014 Genes & development Vol.28 No.12
<P>dsRNA-dependent protein kinase R (PKR) plays a key role in innate immunity. PKR binds viral dsRNA and undergoes autophosphorylation, which leads to translational repression and signaling pathway modulation in infected cells. Kim et al. now show that PKR is activated during mitosis in uninfected cells. PKR interacts with dsRNAs formed by inverted Alu repeats, which become accessible to PKR during mitosis. Phosphorylated PKR then suppresses translation and coordinates mitosis. This study unveils a novel function of PKR and endogenous dsRNA mitosis in uninfected cells.</P>
TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms
Kim, Boseon,Ha, Minju,Loeff, Luuk,Chang, Hyeshik,Simanshu, Dhirendra K,Li, Sisi,Fareh, Mohamed,Patel, Dinshaw J,Joo, Chirlmin,Kim, V Narry John WileySons, Ltd 2015 The EMBO journal Vol.34 No.13
<P>Terminal uridylyl transferases (TUTs) function as integral regulators of microRNA (miRNA) biogenesis. Using biochemistry, single-molecule, and deep sequencing techniques, we here investigate the mechanism by which human TUT7 (also known as ZCCHC6) recognizes and uridylates precursor miRNAs (pre-miRNAs) in the absence of Lin28. We find that the overhang of a pre-miRNA is the key structural element that is recognized by TUT7 and its paralogues, TUT4 (ZCCHC11) and TUT2 (GLD2/PAPD4). For group II pre-miRNAs, which have a 1-nt 3′ overhang, TUT7 restores the canonical end structure (2-nt 3′ overhang) through mono-uridylation, thereby promoting miRNA biogenesis. For pre-miRNAs where the 3′ end is further recessed into the stem (as in 3′ trimmed pre-miRNAs), TUT7 generates an oligo-U tail that leads to degradation. In contrast to Lin28-stimulated oligo-uridylation, which is processive, a distributive mode is employed by TUT7 for both mono- and oligo-uridylation in the absence of Lin28. The overhang length dictates the frequency (but not duration) of the TUT7-RNA interaction, thus explaining how TUT7 differentiates pre-miRNA species with different overhangs. Our study reveals dual roles and mechanisms of uridylation in repair and removal of defective pre-miRNAs.</P>
MicroRNA biogenesis: coordinated cropping and dicing
NATURE PUBLISHING GROUP 2005 NATURE REVIEWS MOLECULAR CELL BIOLOGY Vol.6 No.5
The recent discovery of microRNAs (miRNAs) took many by surprise because of their unorthodox features and widespread functions. These tiny, ∼22-nucleotide, RNAs control several pathways including developmental timing, haematopoiesis, organogenesis, apoptosis, cell proliferation and possibly even tumorigenesis. Among the most pressing questions regarding this unusual class of regulatory miRNA-encoding genes is how miRNAs are produced in cells and how the genes themselves are controlled by various regulatory networks.
Small RNAs just got bigger: Piwi-interacting RNAs (piRNAs) in mammalian testes.
Cold Spring Harbor Laboratory in association with 2006 Genes & development Vol.20 No.15
<P>Small RNAs constitute a large family of regulatory molecules with diverse functions in eukaryotes. Hallmarks of small RNAs are their dependence on double-stranded RNAs (dsRNA)-specific RNase III-type enzymes for biogenesis and their association with Argonaute family proteins for the silencing process. At least two classes of small RNAs have previously been described: microRNAs (miRNAs) derived from hairpin-shaped precursors and small interfering RNAs (siRNAs) generated from long dsRNAs. Recent articles reported a novel class of small RNAs that are expressed specifically and abundantly in the spermatogenic cells of mice. These RNAs are bigger (26-31 nucleotides [nt]) than most previously described small RNAs (21-23 nt) and are associated with Piwi-subclade members of the Argonaute protein family. Although the biogenesis and function of these RNAs are yet to be determined, these findings may add new dimensions in small RNA biology and germline cell biology.</P>
Small RNAs: classification, biogenesis, and function.
Korean Society for Molecular Biology 2005 Molecules and cells Vol.19 No.1
<P>Eukaryotes produce various types of small RNAs of 19-28 nt in length. With rapidly increasing numbers of small RNAs listed in recent years, we have come to realize how widespread their functions are and how diverse the biogenesis pathways have evolved. At the same time, we are beginning to grasp the common features and rules governing the key steps in small RNA pathways. In this review, I will summarize the current classification, biogenesis, action mechanism and function of these fascinating molecules.</P>
Modifications of Small RNAs and Their Associated Proteins
Kim, Young-Kook,Heo, Inha,Kim, V. Narry Elsevier 2010 Cell Vol.143 No.5
<P>Small regulatory RNAs and their associated proteins are subject to diverse modifications that can impinge on their abundance and function. Some of the modifications are under the influence of cellular signaling, thus contributing to the dynamic regulation of RNA silencing.</P>
Elsevier 2008 Cell Vol.133 No.1
<P>Small RNAs carry out their functions by guiding Argonaute (AGO) proteins to their targets. Diverse types of small RNAs and multiple AGO proteins exist in most eukaryotic species, but how small RNAs are sorted into specific AGO complexes remains unclear. Two papers in this issue (<ce:cross-refs refid='bib5 bib6'>Mi et al., 2008; Montgomery et al., 2008</ce:cross-refs>) now reveal the importance of the 5′ terminal nucleotide of the small RNA in the sorting process in <I>Arabidopsis</I>.</P>