scholarly journals Surveillance-ready transcription: nuclear RNA decay as a default fate

Open Biology ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 170270 ◽  
Author(s):  
Stefan Bresson ◽  
David Tollervey
Keyword(s):  
Quality Control ◽  
Rna Decay ◽  
Control Mechanisms ◽  
Protein Coding ◽  
Nuclear Rna ◽  
Rna Quality Control ◽  
Spurious Transcription ◽  
Rna Biogenesis ◽  
Bona Fide ◽  
Nascent Transcripts

Eukaryotic cells synthesize enormous quantities of RNA from diverse classes, most of which are subject to extensive processing. These processes are inherently error-prone, and cells have evolved robust quality control mechanisms to selectively remove aberrant transcripts. These surveillance pathways monitor all aspects of nuclear RNA biogenesis, and in addition remove nonfunctional transcripts arising from spurious transcription and a host of non-protein-coding RNAs (ncRNAs). Surprisingly, this is largely accomplished with only a handful of RNA decay enzymes. It has, therefore, been unclear how these factors efficiently distinguish between functional RNAs and huge numbers of diverse transcripts that must be degraded. Here we describe how bona fide transcripts are specifically protected, particularly by 5′ and 3′ modifications. Conversely, a plethora of factors associated with the nascent transcripts all act to recruit the RNA quality control, surveillance and degradation machinery. We conclude that initiating RNAPII is ‘surveillance ready’, with degradation being a default fate for all transcripts that lack specific protective features. We further postulate that this promiscuity is a key feature that allowed the proliferation of vast numbers of ncRNAs in eukaryotes, including humans.

scholarly journals Integrity of SRP RNA is ensured by La and the nuclear RNA quality control machinery

2014 ◽  
Vol 42 (16) ◽  
pp. 10698-10710 ◽  
Author(s):  
Eileen Leung ◽  
Claudia Schneider ◽  
Fu Yan ◽  
Hatem Mohi-El-Din ◽  
Grzegorz Kudla ◽  
...  
Keyword(s):  
Quality Control ◽  
Rna Quality ◽  
Nuclear Rna ◽  
Rna Quality Control ◽  
Srp Rna

scholarly journals Substrate discrimination and quality control require each catalytic activity of TRAMP and the nuclear RNA exosome

2021 ◽  
Vol 118 (14) ◽  
pp. e2024846118
Author(s):  
Mom Das ◽  
Dimitrios Zattas ◽  
John C. Zinder ◽  
Elizabeth V. Wasmuth ◽  
Julien Henri ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Quality Control ◽  
Catalytic Activity ◽  
Rna Quality ◽  
Data Support ◽  
Nuclear Rna ◽  
Rna Quality Control ◽  
Tramp Complex ◽  
Rna Exosome ◽  
Substrate Discrimination

Quality control requires discrimination between functional and aberrant species to selectively target aberrant substrates for destruction. Nuclear RNA quality control in Saccharomyces cerevisiae includes the TRAMP complex that marks RNA for decay via polyadenylation followed by helicase-dependent 3′ to 5′ degradation by the RNA exosome. Using reconstitution biochemistry, we show that polyadenylation and helicase activities of TRAMP cooperate with processive and distributive exoribonuclease activities of the nuclear RNA exosome to protect stable RNA from degradation while selectively targeting and degrading less stable RNA. Substrate discrimination is lost when the distributive exoribonuclease activity of Rrp6 is inactivated, leading to degradation of stable and unstable RNA species. These data support a proofreading mechanism in which deadenylation by Rrp6 competes with Mtr4-dependent degradation to protect stable RNA while selectively targeting and degrading unstable RNA.

scholarly journals RNA Metabolism Guided by RNA Modifications: The Role of SMUG1 in rRNA Quality Control

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 76
Author(s):  
Lisa Lirussi ◽  
Özlem Demir ◽  
Panpan You ◽  
Antonio Sarno ◽  
Rommie E. Amaro ◽  
...  
Keyword(s):  
Quality Control ◽  
Excision Repair ◽  
Control Mechanisms ◽  
Rna Modifications ◽  
Pseudouridine Synthase ◽  
Repair Enzymes ◽  
Rna Quality Control ◽  
Eukaryotic Dna ◽  
Base Excision ◽  
Post Transcriptional Regulation

RNA modifications are essential for proper RNA processing, quality control, and maturation steps. In the last decade, some eukaryotic DNA repair enzymes have been shown to have an ability to recognize and process modified RNA substrates and thereby contribute to RNA surveillance. Single-strand-selective monofunctional uracil-DNA glycosylase 1 (SMUG1) is a base excision repair enzyme that not only recognizes and removes uracil and oxidized pyrimidines from DNA but is also able to process modified RNA substrates. SMUG1 interacts with the pseudouridine synthase dyskerin (DKC1), an enzyme essential for the correct assembly of small nucleolar ribonucleoproteins (snRNPs) and ribosomal RNA (rRNA) processing. Here, we review rRNA modifications and RNA quality control mechanisms in general and discuss the specific function of SMUG1 in rRNA metabolism. Cells lacking SMUG1 have elevated levels of immature rRNA molecules and accumulation of 5-hydroxymethyluridine (5hmU) in mature rRNA. SMUG1 may be required for post-transcriptional regulation and quality control of rRNAs, partly by regulating rRNA and stability.

scholarly journals Comparative poly(A)+ RNA interactome capture of fission yeast RNA exosome mutants reveals insights into RNA biogenesis

2020 ◽  
Author(s):  
Adrien Birot ◽  
Cornelia Kilchert ◽  
Krzysztof Kus ◽  
Emily Priest ◽  
Ahmad Al Alwash ◽  
...  
Keyword(s):  
Quality Control ◽  
Rna Polymerase Ii ◽  
Rna Binding ◽  
Zinc Finger Protein ◽  
Rna Binding Proteins ◽  
Protein Coding ◽  
Multiple Protein ◽  
Nuclear Rna ◽  
Control Step ◽  
Rna Exosome

ABSTRACTThe nuclear RNA exosome plays a key role in quality control and processing of multiple protein-coding and non-coding transcripts made by RNA polymerase II. A mechanistic understanding of exosome function remains a challenge given it has multiple roles in RNA regulation. Here we have analysed changes in the poly(A)+ RNA transcriptome and interactome provoked by mutations in three distinct subunits of the nuclear RNA exosome. We have identified multiple proteins whose occupancy on RNA is altered in the exosome mutants. We demonstrate that the Zinc-finger protein Mub1 regulates exosome dependent transcripts that encode stress-responsive proteins. Furthermore, we assess impact of the exosome inactivation upon RNA binding of the components of the mRNA processing machineries such as spliceosome and mRNA cleavage polyadenylation complex. We show that mutations in the exosome lead to accumulation of the components of U1 and U2 snRNPs on poly(A)+ RNA and depletion of the components of the activated spliceosome from RNA suggesting that the early stages of spliceosome assembly might provide a critical quality control step. Collectively, our data provide a global view of how RNA metabolism is affected in the exosome-deficient cells and reveal RNA-binding proteins that may act as novel exosome cofactors.

scholarly journals mRNA Editing, Processing and Quality Control in Caenorhabditis elegans

Genetics ◽  
2020 ◽  
Vol 215 (3) ◽  
pp. 531-568
Author(s):  
Joshua A. Arribere ◽  
Hidehito Kuroyanagi ◽  
Heather A. Hundley
Keyword(s):  
Quality Control ◽  
Caenorhabditis Elegans ◽  
Transcription Initiation ◽  
Control Mechanisms ◽  
Mrna Editing ◽  
Protein Coding ◽  
C Elegans ◽  
Expression Of Genes ◽  
Dynamic Expression ◽  
Specific Sequences

While DNA serves as the blueprint of life, the distinct functions of each cell are determined by the dynamic expression of genes from the static genome. The amount and specific sequences of RNAs expressed in a given cell involves a number of regulated processes including RNA synthesis (transcription), processing, splicing, modification, polyadenylation, stability, translation, and degradation. As errors during mRNA production can create gene products that are deleterious to the organism, quality control mechanisms exist to survey and remove errors in mRNA expression and processing. Here, we will provide an overview of mRNA processing and quality control mechanisms that occur in Caenorhabditis elegans, with a focus on those that occur on protein-coding genes after transcription initiation. In addition, we will describe the genetic and technical approaches that have allowed studies in C. elegans to reveal important mechanistic insight into these processes.

Cytosolic protein quality control machinery: Interactions of Hsp70 with a network of co-chaperones and substrates

2021 ◽  
pp. 153537022199981
Author(s):  
Chamithi Karunanayake ◽  
Richard C Page
Keyword(s):  
Quality Control ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Structural Features ◽  
Cellular Protein ◽  
Mechanisms Of Action ◽  
Control Mechanisms ◽  
Nucleotide Exchange ◽  
Domain Organization ◽  
Nucleotide Exchange Factors

The chaperone heat shock protein 70 (Hsp70) and its network of co-chaperones serve as a central hub of cellular protein quality control mechanisms. Domain organization in Hsp70 dictates ATPase activity, ATP dependent allosteric regulation, client/substrate binding and release, and interactions with co-chaperones. The protein quality control activities of Hsp70 are classified as foldase, holdase, and disaggregase activities. Co-chaperones directly assisting protein refolding included J domain proteins and nucleotide exchange factors. However, co-chaperones can also be grouped and explored based on which domain of Hsp70 they interact. Here we discuss how the network of cytosolic co-chaperones for Hsp70 contributes to the functions of Hsp70 while closely looking at their structural features. Comparison of domain organization and the structures of co-chaperones enables greater understanding of the interactions, mechanisms of action, and roles played in protein quality control.

scholarly journals COVID-19 Brings Data Equity Challenges to the Fore

2021 ◽  
Author(s):  
H.V. Jagadish ◽  
Julia Stoyanovich ◽  
Bill Howe
Keyword(s):  
Quality Control ◽  
Government Policy ◽  
Data Driven ◽  
Contact Tracing ◽  
Control Mechanisms ◽  
Sources Of Information ◽  
Decision Systems ◽  
Physical Resources ◽  
Multiple Levels ◽  
Data Driven Decisions

The COVID-19 pandemic is compelling us to make crucial data-driven decisions quickly, bringing together diverse and unreliable sources of information without the usual quality control mechanisms we may employ. These decisions are consequential at multiple levels: they can inform local, state and national government policy, be used to schedule access to physical resources such as elevators and workspaces within an organization, and inform contact tracing and quarantine actions for individuals. In all these cases, significant inequities are likely to arise, and to be propagated and reinforced by data-driven decision systems. In this article, we propose a framework, called FIDES, for surfacing and reasoning about data equity in these systems.

scholarly journals Characterization of the nuclear and cytosolic transcriptomes in human brain tissue reveals new insights into the subcellular distribution of RNA transcripts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ammar Zaghlool ◽  
Adnan Niazi ◽  
Åsa K. Björklund ◽  
Jakub Orzechowski Westholm ◽  
Adam Ameur ◽  
...  
Keyword(s):  
Human Brain ◽  
Expression Analysis ◽  
Differential Expression Analysis ◽  
Adult Brain ◽  
Sequencing Data ◽  
Human Brain Tissue ◽  
Protein Coding ◽  
Rna Transcripts ◽  
Nuclear Rna ◽  
The Impact

AbstractTranscriptome analysis has mainly relied on analyzing RNA sequencing data from whole cells, overlooking the impact of subcellular RNA localization and its influence on our understanding of gene function, and interpretation of gene expression signatures in cells. Here, we separated cytosolic and nuclear RNA from human fetal and adult brain samples and performed a comprehensive analysis of cytosolic and nuclear transcriptomes. There are significant differences in RNA expression for protein-coding and lncRNA genes between cytosol and nucleus. We show that transcripts encoding the nuclear-encoded mitochondrial proteins are significantly enriched in the cytosol compared to the rest of protein-coding genes. Differential expression analysis between fetal and adult frontal cortex show that results obtained from the cytosolic RNA differ from results using nuclear RNA both at the level of transcript types and the number of differentially expressed genes. Our data provide a resource for the subcellular localization of thousands of RNA transcripts in the human brain and highlight differences in using the cytosolic or the nuclear transcriptomes for expression analysis.

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