Volume 139, Issue 1, Pages (October 2009)

Slides:



Advertisements
Similar presentations
Date of download: 7/10/2016 Copyright © 2016 McGraw-Hill Education. All rights reserved. Basic steps of gene expression—transcription factors regulate.
Advertisements

From: Emerging Roles for MicroRNAs in Perioperative Medicine
Schematic representation of the microRNA biogenesis machinery.
Biogenesis of micro (mi) and silencing (si)RNAs
Figure Legend: From: Noncoding RNAs:New Players in Chronic Pain
M. Louise Hull, Victoria Nisenblat  Reproductive BioMedicine Online 
miRNA genomic organization, biogenesis and function
MicroRNA-mediated DNA methylation in plants
Regulation of small RNAs
Long Noncoding RNA in Prostate, Bladder, and Kidney Cancer
Volume 57, Issue 3, Pages (February 2015)
M. Louise Hull, Victoria Nisenblat  Reproductive BioMedicine Online 
Volume 50, Issue 1, Pages (April 2013)
Emerging Roles of RNA Modification: m6A and U-Tail
New Hope for a MicroRNA Therapy for Liver Cancer
Florie Borel, Pavlina Konstantinova, Peter L.M. Jansen 
MicroRNAs: regulators of gene expression and cell differentiation
C. Belair, F. Darfeuille, C. Staedel 
A Happy 3′ Ending to the piRNA Maturation Story
Rafael Kramann, Marcus J. Moeller  Kidney International 
Charon Celine , Moreno Ana Beatriz , Bardou Florian , Crespi Martin  
Benjamin Czech, Gregory J. Hannon  Trends in Biochemical Sciences 
Glen F. Deleavey, Masad J. Damha  Chemistry & Biology 
Volume 29, Issue 6, Pages (June 2014)
MicroRNAs in the Pathogenesis of Lung Cancer
Exosomes in liver pathology
Volume 84, Issue 6, Pages (December 2013)
Toshiaki Watanabe, Haifan Lin  Molecular Cell 
HMGA2, MicroRNAs, and Stem Cell Aging
A Dead End for MicroRNAs
RNA interference: It's a small RNA world
MicroRNAs: Essential players in the regulation of inflammation
Volume 12, Issue 3, Pages (July 2015)
Ars2 and the Cap-Binding Complex Team up for Silencing
Volume 133, Issue 1, Pages (April 2008)
Volume 59, Issue 5, Pages (September 2015)
Mechanisms and Consequences of Alternative Polyadenylation
Volume 125, Issue 5, Pages (June 2006)
A Broadly Conserved Pathway Generates 3′UTR-Directed Primary piRNAs
MicroRNAs in Liver Disease
The Evolution of Antiviral Defense Systems
Gyongyi Szabo, Peter Sarnow, Shashi Bala  Journal of Hepatology 
siRNA Versus miRNA as Therapeutics for Gene Silencing
The Long and Short of MicroRNA
Division of Labor: Minor Splicing in the Cytoplasm
Volume 31, Issue 6, Pages (September 2008)
Baekgyu Kim, Kyowon Jeong, V. Narry Kim  Molecular Cell 
MicroRNA Functions in Stress Responses
A Transcriptome-wide RNAi Screen in the Drosophila Ovary Reveals Factors of the Germline piRNA Pathway  Benjamin Czech, Jonathan B. Preall, Jon McGinn,
MicroRNAs in cancer: biomarkers, functions and therapy
Molecular Therapy - Nucleic Acids
Crosstalk among Histone Modifications
Volume 29, Issue 6, Pages (June 2014)
Small RNA-Mediated Quiescence of Transposable Elements in Animals
Volume 123, Issue 4, Pages (November 2005)
Erica E. Marsh, M. D. , Zhihong Lin, Ph. D. , Ping Yin, Ph. D
A) Primary microRNA (pri-microRNA) is processed by Drosha in the nucleus to form pre-microRNA. a) Primary microRNA (pri-microRNA) is processed by Drosha.
Origins and Mechanisms of miRNAs and siRNAs
Lin28 Mediates the Terminal Uridylation of let-7 Precursor MicroRNA
Markus Bitzer, Iddo Z. Ben-Dov, Thomas Thum  Kidney International 
Small RNAs as Guardians of the Genome
MicroRNA as Therapeutic Targets for Chronic Wound Healing
Modifications of Small RNAs and Their Associated Proteins
Volume 12, Issue 8, Pages (August 2015)
Drug target miRNAs: chances and challenges
Mighty Piwis Defend the Germline against Genome Intruders
MicroRNAs in cancer: biomarkers, functions and therapy
Ancient Endo-siRNA Pathways Reveal New Tricks
Cellular biogenesis of microRNAs.
Stem Cells Neuron Volume 46, Issue 3, Pages (May 2005)
Presentation transcript:

Volume 139, Issue 1, Pages 28-31 (October 2009) Regulating the Regulators: Posttranslational Modifications of RNA Silencing Factors  Inha Heo, V. Narry Kim  Cell  Volume 139, Issue 1, Pages 28-31 (October 2009) DOI: 10.1016/j.cell.2009.09.013 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Small RNA Pathways and the Posttranslational Modification of Silencing Factors (A) MicroRNA biogenesis. The primary transcript of an miRNA gene (pri-miRNA) is cropped into pre-miRNA by Drosha and its cofactor DGCR8. The pre-miRNA is exported to the cytoplasm by exportin 5 and gets processed by Dicer. As a cofactor of Dicer, TRBP stabilizes Dicer and contribute to RISC formation. One strand of the RNA duplex is loaded onto the Ago protein. Four Ago proteins (Ago1–4) are expressed in humans. (B) Phosphorylation of TRBP (HIV-1 TAR RNA-binding protein). TRBP is phosphorylated at serine residues S142, S152, S283, and S286 in response to Erk pathway activity. Phosphorylation of TRBP enhances its stability. Its partner, Dicer, is also stabilized, increasing the levels of this processing complex. Consequently, most miRNAs are upregulated while anti-growth miRNAs, such as let-7 miRNAs, are downregulated through unknown mechanisms. These changes result in cell proliferation and survival. The yellow dots stand for phospho-serine residues in TRBP and green boxes indicate double-stranded RNA-binding domains. (C) Posttranslational modifications of Ago2. The hydroxylase C-P4H(I) catalyzes hydroxylation at proline 700 of Ago2. Proline hydroxylation stabilizes the Ago2 protein, facilitating small RNA-guided mRNA cleavage. In addition, Ago2 is phosphorylated via the p38 MAPK pathway. Serine 387 is the major phosphorylation site. Both the phosphorylation and hydroxylation enhance Ago2 localization to the P body, although the physiological significance of P body localization is unclear. Yellow and blue dots represent phosphorylation site and hydroxylation site, respectively. Orange and blue boxes correspond to PAZ and PIWI domains, respectively. (D) Piwi-interacting RNA biogenesis in mouse testes. piRNAs (24–31 nt) are processed from single-stranded RNA precursors that are transcribed from transposons or large piRNA clusters. Primary processing may occur in the cytoplasm because Miwi and Mili are localized in the cytoplasm. Factors that are needed for primary processing are unknown. In secondary processing, Mili bound to piRNA (sense strand; blue line) cleaves the complementary precursor (antisense strand; red line), defining the 5′ end of a new piRNA. The new piRNA is subsequently passed on to Miwi2. Miwi2, in turn, cleaves the opposite strand precursor, generating the 5′ end of the next piRNA that gets loaded on to Mili. The nuclease that creates the 3′ end of piRNA is unknown. Miwi2 bound to piRNA is transported into the nucleus. (E) Methylation of the Piwi proteins in mice. Piwi proteins are methylated at conserved arginine residues in the N termini by protein methyltransferase PRMT5 and its cofactor WDR77. (Top) Arginines 74, 95, 100, 146, and 163 are methylated in Mili with the major site at arginine 74. Miwi2 has a putative methylation site at the N terminus. Methylated Piwi proteins interact with the indicated Tudor proteins (TDRDs). In fetal testes, TDRD1 induces localization of Miwi2 to a cytoplasmic structure called nuage, which is essential for pre-pachytene piRNA production and transposon silencing. (Bottom) Miwi is methylated at arginines 14 and 49. Although TDRD6 is required for Miwi localization to the chromatoid body, it does not affect pachytene piRNAs. The N termini of Piwi proteins are shown. Red dots stand for experimentally validated methylation sites. (F) Methylation of Piwi proteins in Drosophila. Drosophila Piwi proteins are methylated at conserved arginine residues in the N termini by dPRMT5 and its cofactor valois (Drosophila homolog of WDR77). Arginine methylation promotes Piwi protein stability and consequently increases piRNA levels, resulting in transposon silencing and germ cell development. Orange and blue boxes correspond to PAZ and PIWI domains, respectively. Cell 2009 139, 28-31DOI: (10.1016/j.cell.2009.09.013) Copyright © 2009 Elsevier Inc. Terms and Conditions