Catalytic Properties of the Eukaryotic Exosome

Chlebowski, Aleksander; Tomecki, Rafał; López, María Eugenia Gas; Séraphin, Bertrand; Dziembowski, Andrzej

doi:10.1007/978-1-4419-7841-7_6

Cited by 28 publications

(26 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Catalytic subunits Rrp44 (also known as Dis3) and Rrp6 are bound to core subunits 92 . Rrp6 bound on the cap structure of the RNA exosome core possesses 3′ to 5′ exonuclease activity and Rrp44 bound “under” the ring structure of the core has both 3′ to 5′ exonuclease and endonuclease activities (Figure 3) 93–96 . Although eukaryotic RNA exosome core subunits are highly conserved, recent studies have shown substantial differences in catalytic subunits and cofactors between the yeast and human RNA exosome complexes.…”

Section: The Rna Exosome Complex: Current Understanding Of Structure mentioning

confidence: 99%

RNA Exosome and Non-coding RNA-Coupled Mechanisms in AID-Mediated Genomic Alterations

Laffleur

Basu

Lim

2017

Journal of Molecular Biology

View full text Add to dashboard Cite

The eukaryotic RNA exosome is a well-conserved protein complex with ribonuclease activity implicated in RNA metabolism. Various families of non-coding RNAs (ncRNAs) have been identified as substrates of the complex, underscoring its role as a ncRNA processing/degradation unit. However, the role of RNA exosome and its RNA processing activity on DNA mutagenesis/alteration events have not been investigated until recently. B lymphocytes use two DNA alteration mechanisms, class switch recombination (CSR) and somatic hypermutation (SHM), to re-engineer their antibody gene expressing loci until a tailored antibody gene for a specific antigen is satisfactorily generated. CSR and SHM require the essential activity of the DNA activation induced cytidine deaminase (AID). Causing collateral damage to the B cell genome during CSR and SHM, AID induces unwanted (and sometimes oncogenic) mutations at numerous non-immunoglobulin gene sequences. Recent studies have revealed that AID’s DNA mutator activity is regulated by the RNA exosome complex, thus providing an example of a mechanism that relates DNA mutagenesis with RNA processing. Here, we review the emergent functions of RNA exosome during CSR, SHM and other chromosomal alterations in B cells, and discuss implications relevant to mechanisms that maintain B cell genomic integrity.

show abstract

Section: The Rna Exosome Complex: Current Understanding Of Structure mentioning

confidence: 99%

RNA Exosome and Non-coding RNA-Coupled Mechanisms in AID-Mediated Genomic Alterations

Laffleur

Basu

Lim

2017

Journal of Molecular Biology

View full text Add to dashboard Cite

show abstract

“…DIS3 proteins can be endowed with both processive exonucleolytic and endonucleolytic activities that originate from the RNB and PIN domains, respectively (Lebreton et al 2008;Schaeffer et al 2009;Schneider et al 2009). RRP6 (EXOSC10 in humans) is in turn a distributive exonuclease (Mitchell et al 1997;Chlebowski et al 2010). In yeast, Dis3 is present in both the nucleus and cytoplasm, whereas Rrp6 is restricted to the nucleus.…”

Section: [Supplemental Materials Is Available For This Article]mentioning

confidence: 99%

DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts

et al. 2015

Self Cite

View full text Add to dashboard Cite

Human DIS3, the nuclear catalytic subunit of the exosome complex, contains exonucleolytic and endonucleolytic active domains. To identify DIS3 targets genome-wide, we combined comprehensive transcriptomic analyses of engineered HEK293 cells that expressed mutant DIS3, with Photoactivatable Ribonucleoside-Enhanced Cross-Linking and Immunoprecipitation (PAR-CLIP) experiments. In cells expressing DIS3 with both catalytic sites mutated, RNAs originating from unannotated genomic regions increased ∼2.5-fold, covering ∼70% of the genome and allowing for thousands of novel transcripts to be discovered. Previously described pervasive transcription products, such as Promoter Upstream Transcripts (PROMPTs), accumulated robustly upon DIS3 dysfunction, representing a significant fraction of PAR-CLIP reads. We have also detected relatively long putative premature RNA polymerase II termination products of protein-coding genes whose levels in DIS3 mutant cells can exceed the mature mRNAs, indicating that production of such truncated RNA is a common phenomenon. In addition, we found DIS3 to be involved in controlling the formation of paraspeckles, nuclear bodies that are organized around NEAT1 lncRNA, whose short form was overexpressed in cells with mutated DIS3. Moreover, the DIS3 mutations resulted in misregulation of expression of ∼50% of transcribed protein-coding genes, probably as a secondary effect of accumulation of various noncoding RNA species. Finally, cells expressing mutant DIS3 accumulated snoRNA precursors, which correlated with a strong PAR-CLIP signal, indicating that DIS3 is the main snoRNA-processing enzyme. EXOSC10 (RRP6) instead controls the levels of the mature snoRNAs. Overall, we show that DIS3 has a major nucleoplasmic function in shaping the human RNA polymerase II transcriptome.

show abstract

“…The nuclear and cytoplasmic forms of the eukaryotic exosome complex share ten common subunits [12]. In most organisms, all nine subunits of the exosome core complex are inactive, and enzymatic activities are provided by the tenth catalytic RRP44 subunit, a 3′-5′ hydrolytic exoribinuclease, which also has endonucleolytic activity [13].…”

Section: Introductionmentioning

confidence: 99%

Arabidopsis RRP6L1 and RRP6L2 Function in FLOWERING LOCUS C Silencing via Regulation of Antisense RNA Synthesis

Shin

Chekanova

2014

PLoS Genet

View full text Add to dashboard Cite

The exosome complex functions in RNA metabolism and transcriptional gene silencing. Here, we report that mutations of two Arabidopsis genes encoding nuclear exosome components AtRRP6L1 and AtRRP6L2, cause de-repression of the main flowering repressor FLOWERING LOCUS C (FLC) and thus delay flowering in early-flowering Arabidopsis ecotypes. AtRRP6L mutations affect the expression of known FLC regulatory antisense (AS) RNAs AS I and II, and cause an increase in Histone3 K4 trimethylation (H3K4me3) at FLC. AtRRP6L1 and AtRRP6L2 function redundantly in regulation of FLC and also act independently of the exosome core complex. Moreover, we discovered a novel, long non-coding, non-polyadenylated antisense transcript (ASL, for Antisense Long) originating from the FLC locus in wild type plants. The AtRRP6L proteins function as the main regulators of ASL synthesis, as these mutants show little or no ASL transcript. Unlike ASI/II, ASL associates with H3K27me3 regions of FLC, suggesting that it could function in the maintenance of H3K27 trimethylation during vegetative growth. AtRRP6L mutations also affect H3K27me3 levels and nucleosome density at the FLC locus. Furthermore, AtRRP6L1 physically associates with the ASL transcript and directly interacts with the FLC locus. We propose that AtRRP6L proteins participate in the maintenance of H3K27me3 at FLC via regulating ASL. Furthermore, AtRRP6Ls might participate in multiple FLC silencing pathways by regulating diverse antisense RNAs derived from the FLC locus.

show abstract

Catalytic Properties of the Eukaryotic Exosome

Cited by 28 publications

References 48 publications

RNA Exosome and Non-coding RNA-Coupled Mechanisms in AID-Mediated Genomic Alterations

RNA Exosome and Non-coding RNA-Coupled Mechanisms in AID-Mediated Genomic Alterations

DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts

Arabidopsis RRP6L1 and RRP6L2 Function in FLOWERING LOCUS C Silencing via Regulation of Antisense RNA Synthesis

Contact Info

Product

Resources

About