Noncoding RNAs and Gene Silencing

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Noncoding RNAs and Gene Silencing Mikel Zaratiegui, Danielle V. Irvine, Robert A. Martienssen  Cell  Volume 128, Issue 4, Pages 763-776 (February 2007) DOI: 10.1016/j.cell.2007.02.016 Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 1 Repeat Structure of the Centromere in Different Organisms (A) The chromosome III centromere of S. pombe consists of repeated dg and dh motifs around a unique central region flanked by inverted imr repeats. (B) Human centromeres are mainly composed of tandem arrays of α-satellite DNA repeats that span several megabases. A central region (right section) is composed of chromosome-specific higher order motifs composed of related α-satellite repeats, and is flanked by more heterogeneous and disordered repeats interspersed by LINEs and SINEs (left section) adapted from Schueler and Sullivan (2006). (C) Arabidopsis centromeres display long arrays of 180 type satellites interspersed by LTR retrotransposons and LTR-derived 106B repeats (adapted from May et al. [2005]). (D) Drosophila centromeres are composed of long homogeneous satellite regions, with inserted LTR retrotransposons (red and yellow sections), that flank a complex region composed of fragments of TEs arranged in direct and inverted orientations (adapted from Sun et al. [2003]). Cell 2007 128, 763-776DOI: (10.1016/j.cell.2007.02.016) Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 2 Models of MSUD RNA-Silencing Pathways (A) During the sexual phase of the Neurospora life cycle, any transcribed region of DNA that has failed to pair in the homolog pairing stage is silenced in a process called MSUD. In this pathway, unpaired DNA is transcribed by an unknown DNA-dependent RNA polymerase to produce a transcript that is processed into dsRNA by the RdRP Sad-1. siRNAs produced by Sms-3 dicing of dsRNA are incorporated into a putative RISC complex containing Sms-2, a Paz/Piwi domain-containing protein. The RISC complex guided by siRNA acts in the degradation of homologous mRNA. (B) During meiosis in C. elegans, unsynapsed chromosomes and chromosomal regions are silenced by a mechanism with parallels to MSUD. Unpaired chromosomal regions are transcribed and the transcripts are processed into dsRNA by the germline-specific RdRP ego-1. The single C. elegans dicer, DCL-1, is not involved in processing these dsRNAs. It is unknown whether siRNAs are produced from these dsRNAs (by an unidentified enzyme) or whether the long RNA transcripts themselves act as guides for H3K9 methylation of the unpaired regions. Cell 2007 128, 763-776DOI: (10.1016/j.cell.2007.02.016) Copyright © 2007 Elsevier Inc. Terms and Conditions

Figure 3 Silencing Transcripts at the S. pombe Centromere and Different Transcript-Mediated Silencing Systems (A) S. pombe dg-imr transcript in centromere IL. The forward promoter is silenced by constitutive transcription and processing into siRNA of the reverse strand. (B) The X inactivation center has several noncoding transcripts, and transcription of Tsix silences the Xist promoter. (C and D) Paternal locus transcription of noncoding transcripts Kcnq1ot and Air influences the expression of overlapping and nonoverlapping genes in the imprinted gene cluster at the telomeric end of mouse chromosome 7 and the Igf2r locus, respectively. Paternally expressed genes are colored blue, maternally expressed genes are colored red, and ubiquitously expressed genes are colored green. Cell 2007 128, 763-776DOI: (10.1016/j.cell.2007.02.016) Copyright © 2007 Elsevier Inc. Terms and Conditions