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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.
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>
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.
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>
Biogenesis of small RNAs in animals
Kim, V. Narry,Han, Jinju,Siomi, Mikiko C. Nature Publishing Group 2009 NATURE REVIEWS MOLECULAR CELL BIOLOGY Vol.10 No.2
Small RNAs of 20–30 nucleotides can target both chromatin and transcripts, and thereby keep both the genome and the transcriptome under extensive surveillance. Recent progress in high-throughput sequencing has uncovered an astounding landscape of small RNAs in eukaryotic cells. Various small RNAs of distinctive characteristics have been found and can be classified into three classes based on their biogenesis mechanism and the type of Argonaute protein that they are associated with: microRNAs (miRNAs), endogenous small interfering RNAs (endo-siRNAs or esiRNAs) and Piwi-interacting RNAs (piRNAs). This Review summarizes our current knowledge of how these intriguing molecules are generated in animal cells.
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>
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>