scholarly journals A conserved RNA degradation complex required for spreading and epigenetic inheritance of heterochromatin

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Gergana Shipkovenska ◽  
Alexander Durango ◽  
Marian Kalocsay ◽  
Steven P Gygi ◽  
Danesh Moazed
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
Rna Degradation ◽  
Heterochromatin Formation ◽  
Polynucleotide Kinase ◽  
Ribosomal Rna Processing ◽  
Formation System ◽  
Insight Into

Heterochromatic domains containing histone H3 lysine 9 methylation (H3K9me) can be epigenetically inherited independently of underlying DNA sequence. To gain insight into the mechanisms that mediate epigenetic inheritance, we used a Schizosaccharomyces pombe inducible heterochromatin formation system to perform a genetic screen for mutations that abolish heterochromatin inheritance without affecting its establishment. We identified mutations in several pathways, including the conserved and essential Rix1-associated complex (henceforth the rixosome), which contains RNA endonuclease and polynucleotide kinase activities with known roles in ribosomal RNA processing. We show that the rixosome is required for spreading and epigenetic inheritance of heterochromatin in fission yeast. Viable rixosome mutations that disrupt its association with Swi6/HP1 fail to localize to heterochromatin, lead to accumulation of heterochromatic RNAs, and block spreading of H3K9me and silencing into actively transcribed regions. These findings reveal a new pathway for degradation of heterochromatic RNAs with essential roles in heterochromatin spreading and inheritance.

scholarly journals An RNA Degradation Complex Required for Spreading and Epigenetic Inheritance of Heterochromatin

2019 ◽  
Author(s):  
Gergana Shipkovenska ◽  
Alexander Durango ◽  
Marian Kalocsay ◽  
Steven P. Gygi ◽  
Danesh Moazed
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Ribosomal Rna ◽  
Histone H3 ◽  
Epigenetic Inheritance ◽  
Rna Degradation ◽  
Rrna Processing ◽  
Nucleation Sites ◽  
Polynucleotide Kinase ◽  
Heterochromatin Assembly

AbstractHeterochromatin assembly requires the methylation of histone H3 lysine 9 by the Clr4(Suv39h) methyltransferase and both the spreading and epigenetic inheritance of heterochromatin involve the recognition of H3K9me-containing nucleosomes by Clr4 and catalysis of H3K9me on adjacent nucleosomes. How this read-write mechanism overcomes obstacles posed by RNA polymerase II and nascent RNA in its path is not fully understood. Here we identify a role for the highly conserved and essential Rix1-containing complex (here referred to as the rixosome), with known RNA endonuclease and polynucleotide kinase activities required for ribosomal RNA (rRNA) processing, in spreading and epigenetic inheritance of heterochromatin. Viable mutations in rixosome subunits that disrupt its association with Swi6/HP1 fail to localize to heterochromatin, lead to accumulation of heterochromatic RNAs, and block spreading of H3K9me and silencing away from nucleation sites into actively transcribed regions. These findings reveal a new pathway for degradation of heterochromatic RNAs with essential roles in heterochromatin spreading and inheritance.

scholarly journals Both endonucleolytic and exonucleolytic cleavage mediate ITS1 removal during human ribosomal RNA processing

2013 ◽  
Vol 200 (5) ◽  
pp. 577-588 ◽  
Author(s):  
Katherine E. Sloan ◽  
Sandy Mattijssen ◽  
Simon Lebaron ◽  
David Tollervey ◽  
Ger J.M. Pruijn ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Large Subunit ◽  
Genetic Diseases ◽  
Evolutionary Conservation ◽  
Rrna Processing ◽  
Ribosomal Subunits ◽  
Important Pathway ◽  
Ribosomal Rna Processing ◽  
Insight Into

Human ribosome production is up-regulated during tumorogenesis and is defective in many genetic diseases (ribosomopathies). We have undertaken a detailed analysis of human precursor ribosomal RNA (pre-rRNA) processing because surprisingly little is known about this important pathway. Processing in internal transcribed spacer 1 (ITS1) is a key step that separates the rRNA components of the large and small ribosomal subunits. We report that this was initiated by endonuclease cleavage, which required large subunit biogenesis factors. This was followed by 3′ to 5′ exonucleolytic processing by RRP6 and the exosome, an enzyme complex not previously linked to ITS1 removal. In contrast, RNA interference–mediated knockdown of the endoribonuclease MRP did not result in a clear defect in ITS1 processing. Despite the apparently high evolutionary conservation of the pre-rRNA processing pathway and ribosome synthesis factors, each of these features of human ITS1 processing is distinct from those in budding yeast. These results also provide significant insight into the links between ribosomopathies and ribosome production in human cells.

scholarly journals Structural insight into precursor ribosomal RNA processing by ribonuclease MRP

Science ◽  
2020 ◽  
Vol 369 (6504) ◽  
pp. 656-663 ◽  
Author(s):  
Pengfei Lan ◽  
Bin Zhou ◽  
Ming Tan ◽  
Shaobai Li ◽  
Mi Cao ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Cell Cycle Regulation ◽  
Consensus Sequence ◽  
Rrna Processing ◽  
Rnase Mrp ◽  
Cryo Electron Microscopy ◽  
Ribosomal Rna Processing ◽  
Cycle Regulation ◽  
Insight Into

Ribonuclease (RNase) MRP is a conserved eukaryotic ribonucleoprotein complex that plays essential roles in precursor ribosomal RNA (pre-rRNA) processing and cell cycle regulation. In contrast to RNase P, which selectively cleaves transfer RNA–like substrates, it has remained a mystery how RNase MRP recognizes its diverse substrates. To address this question, we determined cryo–electron microscopy structures of Saccharomyces cerevisiae RNase MRP alone and in complex with a fragment of pre-rRNA. These structures and the results of biochemical studies reveal that coevolution of both protein and RNA subunits has transformed RNase MRP into a distinct ribonuclease that processes single-stranded RNAs by recognizing a short, loosely defined consensus sequence. This broad substrate specificity suggests that RNase MRP may have myriad yet unrecognized substrates that could play important roles in various cellular contexts.

scholarly journals An RNA degradation complex required for silencing of Polycomb target genes

2019 ◽  
Author(s):  
Haining Zhou ◽  
Gergana Shipkovenska ◽  
Marian Kalocsay ◽  
Jiuchun Zhang ◽  
Zhenhua Luo ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Target Genes ◽  
Cellular Proliferation ◽  
Embryonic Stem ◽  
Rna Degradation ◽  
Chromatin Binding ◽  
Chromatin Compaction ◽  
Condensate Formation ◽  
Ribosomal Rna Processing

AbstractPolycomb Repressive Complex (PRC) 1 and 2 are histone-modifying and chromatin-binding complexes that are required for silencing of developmental regulatory genes and genes that control cellular proliferation. Their gene silencing functions are thought to involve chromatin compaction and condensate formation but whether other mechanisms contribute to silencing is unknown. Here we show that the rixosome, a conserved RNA degradation complex with roles in ribosomal RNA processing and heterochromatic RNA degradation in fission yeast, associates with human PRC complexes, is recruited to promoters of Polycomb target genes in differentiated cell lines and embryonic stem cells, and is required for efficient silencing of Polycomb target genes. These findings reveal an unanticipated role for RNA degradation in Polycomb-mediated silencing.

Adenovirus infection retards ribosomal RNA processing

1989 ◽  
Vol 138 (1) ◽  
pp. 205-207 ◽  
Author(s):  
Susan H. Lawler ◽  
Robert W. Jones ◽  
Brian P. Eliceiri ◽  
George L. Eliceiri
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Adenovirus Infection ◽  
Ribosomal Rna Processing

Developmental expression of fibrillarin and U3 snRNA in Xenopus laevis

Development ◽  
1991 ◽  
Vol 112 (1) ◽  
pp. 317-326
Author(s):  
M. Caizergues-Ferrer ◽  
C. Mathieu ◽  
P. Mariottini ◽  
F. Amalric ◽  
F. Amaldi
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Protein Detection ◽  
Developmental Expression ◽  
Oocyte Growth ◽  
Small Nuclear Ribonucleoprotein ◽  
Hybridization Probes ◽  
Ribosomal Rna Processing ◽  
Protein Components ◽  
Nuclear Ribonucleoprotein

Fibrillarin is one of the protein components that together with U3 snRNA constitute the U3 snRNP, a small nuclear ribonucleoprotein particle involved in ribosomal RNA processing in eucaryotic cells. Using an antifibrillarin antiserum for protein detection and a fibrillarin cDNA and a synthetic oligonucleotide complementary to U3 snRNA as hybridization probes, the expression of these two components has been studied during Xenopus development. Fibrillarin mRNA is accumulated early in oogenesis, like many other messengers, and translated during oocyte growth. Fibrillarin protein is thus progressively accumulated throughout oogenesis to be assembled with U3 snRNA and used for ribosome production in the amplified nucleoli. After fertilization, the amount of U3 snRNA decreases while the maternally accumulated fibrillarin mRNA is maintained and utilized to produce more protein. After the mid-blastula transition, stored fibrillarin is assembled with newly synthesized U3 snRNA and becomes localized in the prenucleolar bodies and reforming nucleoli.

Defect in pre-ribosomal RNA processing is involved in myeloid leukemogenesis

2015 ◽  
Vol 43 (9) ◽  
pp. S78
Author(s):  
Hirotaka Matsui ◽  
Akinori Kanai ◽  
Akiko Nagamachi ◽  
Moe Okuno ◽  
Toshiya Inaba
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Ribosomal Rna Processing
Sign in / Sign up

Export Citation Format

Share Document