scholarly journals InsP7is a small-molecule regulator of NUDT3-mediated mRNA decapping and processing-body dynamics

2020 ◽  
Vol 117 (32) ◽  
pp. 19245-19253 ◽  
Author(s):  
Soumyadip Sahu ◽  
Zhenzhen Wang ◽  
Xinfu Jiao ◽  
Chunfang Gu ◽  
Nikolaus Jork ◽  
...  
Keyword(s):  
Stress Responses ◽  
Messenger Rna ◽  
Control Process ◽  
Stem Cell Differentiation ◽  
Wild Type ◽  
Inositol Pyrophosphate ◽  
Body Dynamics ◽  
Processing Body ◽  
The Stability

Regulation of enzymatic 5′ decapping of messenger RNA (mRNA), which normally commits transcripts to their destruction, has the capacity to dynamically reshape the transcriptome. For example, protection from 5′ decapping promotes accumulation of mRNAs into processing (P) bodies—membraneless, biomolecular condensates. Such compartmentalization of mRNAs temporarily removes them from the translatable pool; these repressed transcripts are stabilized and stored until P-body dissolution permits transcript reentry into the cytosol. Here, we describe regulation of mRNA stability and P-body dynamics by the inositol pyrophosphate signaling molecule 5-InsP7(5-diphosphoinositol pentakisphosphate). First, we demonstrate 5-InsP7inhibits decapping by recombinant NUDT3 (Nudix [nucleoside diphosphate linked moiety X]-type hydrolase 3) in vitro. Next, in intact HEK293 and HCT116 cells, we monitored the stability of a cadre of NUDT3 mRNA substrates following CRISPR-Cas9 knockout ofPPIP5Ks(diphosphoinositol pentakisphosphate 5-kinases type 1 and 2, i.e.,PPIP5KKO), which elevates cellular 5-InsP7levels by two- to threefold (i.e., within the physiological rheostatic range). ThePPIP5KKO cells exhibited elevated levels of NUDT3 mRNA substrates and increased P-body abundance. Pharmacological and genetic attenuation of 5-InsP7synthesis in the KO background reverted both NUDT3 mRNA substrate levels and P-body counts to those of wild-type cells. Furthermore, liposomal delivery of a metabolically resistant 5-InsP7analog into wild-type cells elevated levels of NUDT3 mRNA substrates and raised P-body abundance. In the context that cellular 5-InsP7levels normally fluctuate in response to changes in the bioenergetic environment, regulation of mRNA structure by this inositol pyrophosphate represents an epitranscriptomic control process. The associated impact on P-body dynamics has relevance to regulation of stem cell differentiation, stress responses, and, potentially, amelioration of neurodegenerative diseases and aging.

scholarly journals DNA Damage–Induced BARD1 Phosphorylation Is Critical for the Inhibition of Messenger RNA Processing by BRCA1/BARD1 Complex

2006 ◽  
Vol 66 (9) ◽  
pp. 4561-4565 ◽  
Author(s):  
Ho-Shik Kim ◽  
Hongjie Li ◽  
Murat Cevher ◽  
Alissa Parmelee ◽  
Danae Fonseca ◽  
...  
Keyword(s):  
Dna Damage ◽  
Rna Processing ◽  
Messenger Rna

scholarly journals Pre-Messenger RNA Processing Factors in the Drosophila Genome

2000 ◽  
Vol 150 (2) ◽  
pp. F37-F44 ◽  
Author(s):  
Stephen M. Mount ◽  
Helen K. Salz
Keyword(s):  
Rna Processing ◽  
Messenger Rna ◽  
Drosophila Genome ◽  
Processing Factors

scholarly journals A dual reporter approach to quantify defects in messenger RNA processing

2009 ◽  
Vol 395 (2) ◽  
pp. 237-243 ◽  
Author(s):  
Ayan Banerjee ◽  
Mimi C. Sammarco ◽  
Scott Ditch ◽  
Ed Grabczyk
Keyword(s):  
Rna Processing ◽  
Messenger Rna ◽  
Dual Reporter

Messenger RNA Processing in Eukaryotes

2013 ◽  
pp. 59-64
Author(s):  
K. Potter ◽  
N. Cremona ◽  
J.A. Wise
Keyword(s):  
Rna Processing ◽  
Messenger Rna

scholarly journals Nuclear RNA-protein interactions and messenger RNA processing.

1983 ◽  
Vol 97 (5) ◽  
pp. 1321-1326 ◽  
Author(s):  
T Pederson
Keyword(s):  
Detailed Analysis ◽  
Recent Work ◽  
Protein Interactions ◽  
Rna Processing ◽  
Messenger Rna ◽  
Mammalian Cells ◽  
General Hypothesis ◽  
Ribonucleoprotein Particles ◽  
Nuclear Rna ◽  
Nuclear Ribonucleoprotein

Eucaryotic messenger RNA precursors are processed in nuclear ribonucleoprotein particles (hnRNP). Here recent work on the structure of hnRNP is reviewed, with emphasis on function. Detailed analysis of a specific case, the altered assembly of hnRNP in heat-shocked Drosophila and mammalian cells, leads to a general hypothesis linking hnRNP structure and messenger RNA processing.

Ultrastructural analysis of early pre-messenger RNA processing events using the Miller chromatin spreading method

1992 ◽  
Vol 50 (1) ◽  
pp. 554-555
Author(s):  
Ann Beyer ◽  
Yvonne Osheim
Keyword(s):  
Rna Processing ◽  
Messenger Rna ◽  
Structural Features ◽  
Ultrastructural Analysis ◽  
Electron Microscopic ◽  
Mrna Transcripts ◽  
Carbon Coated ◽  
Nascent Transcripts ◽  
Active Genes

We use the Miller chromatin spreading technique for electron microscopic visualization of transcriptionally active genes. In this method, cells are hypotonically disrupted and cellular contents are diluted into water at pH 8-9 and fixed with formaldehyde. The dispersed cellular contents are centrifuged onto a carbon-coated EM grid; the majority of the material that is deposited on the grid consists of entangled masses of dispersed chromatin, some regions of which are transcriptionally active (Fig 1). Our interests lie in ultrastructural analysis of co-transcriptional RNA processing events on pre-mRNA transcripts, which we analyze by mapping structural features on successive nascent transcripts on a given gene. The two processing events that we have been able to study by this approach are the removal of introns by splicing and generation of the 3’ end of the transcript.

An RNA exosome subunit mediates cell-to-cell trafficking of a homeobox mRNA via plasmodesmata

Science ◽  
2022 ◽  
Vol 375 (6577) ◽  
pp. 177-182
Author(s):  
Munenori Kitagawa ◽  
Peipei Wu ◽  
Rachappa Balkunde ◽  
Patrick Cunniff ◽  
David Jackson
Keyword(s):  
Ribosomal Rna ◽  
Rna Processing ◽  
Messenger Rna ◽  
Plant Cells ◽  
Cell Trafficking ◽  
Cell Transport ◽  
Homeobox Transcription Factor ◽  
A Subunit ◽  
Ribosomal Rna Processing ◽  
Rna Exosome

mRNA migration through plasmodesmata In plants, certain transcription factors are produced in one cell but transported, sometimes as messenger RNA (mRNA), through plasmodesmata, channels between neighboring plant cells, where they act. This system helps to manage stem cell development. Kitagawa et al . now identify part of the machinery that manages this cell-to-cell transport. Transport of the mRNA encoding the KNOTTED1 homeobox transcription factor depends on Ribosomal RNA-Processing Protein 44 (AtRRP44A), which is a subunit of the RNA exosome. —PJH

Abstract 842: Messenger RNA Processing Body Participates In Cardiac Protection Induced By Heat Shock Preconditioning In Mouse Hearts

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Chang Yin ◽  
Rakesh C Kukreja
Keyword(s):  
Heat Shock ◽  
Messenger Rna ◽  
Micro Rna ◽  
Protective Mechanism ◽  
Body Formation ◽  
New Strategy ◽  
Body Components ◽  
Processing Body ◽  
Cardiac Preconditioning

mRNA Processing Body (P-Body) is a specialized cytoplasmic structure that functions as a major site for post-transcriptional and trnanslational repression. Target mRNA is guided into P-Body through base-pairing with its micro-RNA (miRNA), where they further bind to P-Body components such as GW182 and AGO2; thus get retained away from translation machinery or degraded. Our previous study detected an increase of a key component of P-Body, miRNA, in heat-shock (HS) protected hearts. To gain further insights into the protective mechanism, we hypothesized that the miRNA-associated protection is mediated through P-Body formation. This hypothesis was tested by measuring three key components of P-Body, i.e., miRNA (target seeker), GW182 (marker of P-Body, also called GW-Body) and AGO2 (mRNA catalytic enzyme). METHODS : ICR mice were either HS-preconditioned (15 min, 42°C, anal temperature) or kept at room temperature (controls). miRNA and proteins were extracted 2 hour after HS. miRNA induction was verified by RT-PCR. P-Body formation was evaluated by measuring the binding of GW182 and AGO2, using a combination of immunopricipitation and Western blotting techniques. To study the role of miRNA in P-Body formation, identical experiments were also repeated in mice treated with miRNA-1 inhibitor (antisense miRNA-1 with 2′-O-methyl base at every nucleotide). RESULTS : Compared to the control, HS-preconditioning significantly induced miRNA-1 (150 ± 11%, mean ± SEM), miRNA-21 (71 ± 10%) and miRNA-24 (68 ± 14%). GW182 (109 ± 16%) and AGO2 (50 ± 16%) were also increased in the HS-group. More importantly, there was an increase (39 ± 11%) in co-immunopricipitation between GW182 and AGO2 in the HS-group than in the control, indicating more binding of the two key P-Body components. However, this co-immunoprecipitation was significantly reduced (−68 ± 8%) in the mice treated with the miRNA-1 inhibitor after HS. CONCLUSION : The formation of P-Body following HS-preconditioning represents a novel protective pathway against ischemic injury. The pharmaceutical potential of P-Body formation may offer a new strategy in cardiac preconditioning.

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