scholarly journals Widespread interaction between ADAR1 and transcriptional byproducts

2019 ◽  
Author(s):  
Chan-Shuo Wu ◽  
Sze Jing Tang ◽  
Hong Kee Tan ◽  
Li-Yuan Hung ◽  
Wei Wen Teo ◽  
...  
Keyword(s):  
Rna Editing ◽  
Rna Binding ◽  
Rna Biology ◽  
Rna Immunoprecipitation ◽  
Intergenic Regions ◽  
Rna Fragments ◽  
Exon Junctions ◽  
Editing Enzyme

AbstractBackgroundADAR1, an adenosine-to-inosine (A-to-I) RNA editing enzyme, has an emerging role in cancer immunotherapy. ADAR1 presumably works by suppressing cellular innate immunity response to endogenously generated double-stranded RNAs through RNA editing. However, RNA species that are directly regulated by ADAR1 mediated RNA editing processes remain poorly defined.ResultsIn this study, we used a novel bioinformatics approach to track ADAR1-RNA interactions. By integrating DNA-seq, RNA-seq, and ADAR1 RNA immunoprecipitation sequencing (fRIP-seq) data of K562 cell line, we provided the first in-situ landscape profiling of ADAR1 RNA binding and editing activities. With long RNA fragments captured by ADAR1 immunoprecipitation, we were able to identify exon junctions and genomic boundaries used by ADAR1-associated RNAs and thus we could possibly trace pre-RNA processing steps that had been acting on them. Our methodology allowed us to acquire the knowledge of transcriptome-wide scenario of ADAR1 activities. Intriguingly, we found that ADAR1 had a tendency to interact with transcriptional byproducts originated from obscure regions such as introns and intergenic regions.ConclusionsOur observation might shed light on the dual role of ADAR1 proteins not only in diversifying the transcriptome, but also in reigning RNA debris from obscure regions. Moreover, as the functional potential of seemly transcriptional byproducts is just beginning to emerge, this study would bridge ADAR1 with other fields of RNA biology.

scholarly journals Chromosomal Storage of the RNA-editing Enzyme ADAR1 in Xenopus Oocytes

2005 ◽  
Vol 16 (7) ◽  
pp. 3377-3386 ◽  
Author(s):  
Nina B. Sallacz ◽  
Michael F. Jantsch
Keyword(s):  
Rna Editing ◽  
Binding Sites ◽  
Rna Binding ◽  
Adenosine Deaminases ◽  
A Site ◽  
Nascent Transcripts ◽  
Editing Enzyme ◽  
Nuclear Injection ◽  
Processing Factors

ADARs (adenosine deaminases that act on RNA) are RNA-editing enzymes that convert adenosines to inosines in structured or double-stranded RNAs. Expression and intracellular distribution of ADAR1 is controlled by a plethora of mechanisms suggesting that enzyme activity has to be tightly regulated. Mammalian ADAR1 is a shuttling protein, whereas Xenopus ADAR1 is exclusively nuclear. In oocytes, Xenopus ADAR1 associates with most nascent transcripts but is strongly enriched at a specific site on chromosome 3, termed the special loop. Enrichment at this site requires the presence of RNAs but is independent of ongoing transcription. Here we show that RNAs transcribed elsewhere in the genome accumulate at the special loop even in the absence of transcription. In situ hybridization experiments, however, indicate the absence of known editing substrates from this site. In the absence of transcription also other RNA binding and processing factors accumulate at the special loop, suggesting that ADAR1 is stored or assembled at the special loop in an RNA-containing complex. Nuclear injection of RNAs providing binding sites for ADAR1 dissociates the enzyme from the special loop, supporting the notion that the special loop represents a site where ADAR1 is stored, possibly for later use during development.

PC.01.7 AN ESSENTIAL ROLE OF RNA EDITING ENZYME ADAR1 IN COELIAC DISEASE MUCOSA

2021 ◽  
Vol 53 ◽  
pp. S90
Author(s):  
M.T. Segreto ◽  
D. Di Fusco ◽  
S. Sessa ◽  
G. Di Maggio ◽  
C. Maresca ◽  
...  
Keyword(s):  
Coeliac Disease ◽  
Rna Editing ◽  
Essential Role ◽  
Editing Enzyme

scholarly journals TRIBE: Hijacking an RNA-Editing Enzyme to Identify Cell-Specific Targets of RNA-Binding Proteins

Cell ◽  
2016 ◽  
Vol 165 (3) ◽  
pp. 742-753 ◽  
Author(s):  
Aoife C. McMahon ◽  
Reazur Rahman ◽  
Hua Jin ◽  
James L. Shen ◽  
Allegra Fieldsend ◽  
...  
Keyword(s):  
Rna Editing ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Editing Enzyme

scholarly journals ADAR1 can drive Multiple Myeloma progression by acting both as an RNA editor of specific transcripts and as a DNA mutator of their cognate genes

2020 ◽  
Author(s):  
Rafail Nikolaos Tasakis ◽  
Alessandro Laganà ◽  
Dimitra Stamkopoulou ◽  
David T. Melnekoff ◽  
Pavithra Nedumaran ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Rna Editing ◽  
Mutational Signatures ◽  
Dna Mutation ◽  
Over Expression ◽  
Dna Mutations ◽  
Poor Outcomes ◽  
Editing Enzyme ◽  
Chromosome 1Q21

ABSTRACTRNA editing is an epitranscriptomic modification of emerging relevance to disease development and manifestations. ADAR1, which resides on human chromosome 1q21, is an RNA editor whose over-expression, either by interferon (IFN) induction or through gene amplification, is associated with increased editing and poor outcomes in Multiple Myeloma (MM). Here we explored the role of ADAR1 in the context of MM progression, by focusing on a group of 23 patients in the MMRF CoMMpass Study for which RNAseq and WES datasets exist for matched pre-and post-relapse samples. Our analysis reveals an acquisition of new DNA mutations on disease progression at specific loci surrounding the sites of ADAR associated (A-to-I) RNA editing. These analyses suggest that the RNA editing enzyme ADAR1 can function as a DNA mutator during Multiple Myeloma (MM) progression, and further imply that guide-targeted RNA editing has the capacity to generate specific mutational signatures at predetermined locations. This dual role of RNA editor and DNA mutator might be shared by other deaminases, such as APOBECs, so that DNA mutation might be the result of collateral damage on the genome by an editing enzyme whose primary job is to re-code the cognate transcript toward specific functional outcomes.

scholarly journals Architectural RNA in chromatin organization

2020 ◽  
Vol 48 (5) ◽  
pp. 1967-1978
Author(s):  
Jitendra Thakur ◽  
Steven Henikoff
Keyword(s):  
Rna Binding ◽  
Rna Binding Proteins ◽  
Ribonuclease A ◽  
Rnase A ◽  
Chromatin Organization ◽  
Nuclear Bodies ◽  
Non Coding Rnas ◽  
Rna Depletion

RNA plays a well-established architectural role in the formation of membraneless interchromatin nuclear bodies. However, a less well-known role of RNA is in organizing chromatin, whereby specific RNAs have been found to recruit chromatin modifier proteins. Whether or not RNA can act as an architectural molecule for chromatin remains unclear, partly because dissecting the architectural role of RNA from its regulatory role remains challenging. Studies that have addressed RNA's architectural role in chromatin organization rely on in situ RNA depletion using Ribonuclease A (RNase A) and suggest that RNA plays a major direct architectural role in chromatin organization. In this review, we will discuss these findings, candidate chromatin architectural long non-coding RNAs and possible mechanisms by which RNA, along with RNA binding proteins might be mediating chromatin organization.

scholarly journals LncRNA AC245100.4 binds HSP90 to promote the proliferation of prostate cancer

Epigenomics ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1257-1271
Author(s):  
Rongjun Cui ◽  
Chi Liu ◽  
Ping Lin ◽  
Hui Xie ◽  
Wei Wang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Counting ◽  
Chaperone Function ◽  
In Vivo Assays ◽  
Iκb Kinase ◽  
Rna Immunoprecipitation ◽  
The Stability

Aim: To investigate the role and mechanisms of AC245100.4 in prostate cancer. Materials & methods: The expression and location of AC245100.4 were examined using real-time PCR and  in situ hybridization. Cell Counting Kit-8, clone formation, flow cytometry and in vivo assays were conducted to determine the role of AC245100.4. RNA antisense purification with mass spectrometry and RNA immunoprecipitation were performed to identify proteins that bind to AC245100.4. Western blotting was performed to quantify the expression of protein. Results: AC245100.4 expression was upregulated in prostate cancer and mainly located in the cytoplasm. Knockdown of AC245100.4 inhibited proliferation of prostate cancer. Mechanistically, AC245100.4 bound to HSP90 and altered its chaperone function, increased the stability of IκB kinase and activated the NFκB signaling pathway. Conclusion: AC245100.4 promotes the proliferation of prostate cancer via binding of HSP90.

scholarly journals Distinct in vivo roles for double-stranded RNA-binding domains of the Xenopus RNA-editing enzyme ADAR1 in chromosomal targeting

2003 ◽  
Vol 161 (2) ◽  
pp. 309-319 ◽  
Author(s):  
Michael Doyle ◽  
Michael F. Jantsch
Keyword(s):  
Rna Editing ◽  
Rna Binding ◽  
Double Stranded Rna ◽  
Binding Domains ◽  
Initial Substrate ◽  
Rna Binding Domains ◽  
Editing Enzyme ◽  
Deaminase Domain

The RNA-editing enzyme adenosine deaminase that acts on RNA (ADAR1) deaminates adenosines to inosines in double-stranded RNA substrates. Currently, it is not clear how the enzyme targets and discriminates different substrates in vivo. However, it has been shown that the deaminase domain plays an important role in distinguishing various adenosines within a given substrate RNA in vitro. Previously, we could show that Xenopus ADAR1 is associated with nascent transcripts on transcriptionally active lampbrush chromosomes, indicating that initial substrate binding and possibly editing itself occurs cotranscriptionally. Here, we demonstrate that chromosomal association depends solely on the three double-stranded RNA-binding domains (dsRBDs) found in the central part of ADAR1, but not on the Z-DNA–binding domain in the NH2 terminus nor the catalytic deaminase domain in the COOH terminus of the protein. Most importantly, we show that individual dsRBDs are capable of recognizing different chromosomal sites in an apparently specific manner. Thus, our results not only prove the requirement of dsRBDs for chromosomal targeting, but also show that individual dsRBDs have distinct in vivo localization capabilities that may be important for initial substrate recognition and subsequent editing specificity.

An essential role of RNA editing enzyme ADAR1 in mouse skin

2011 ◽  
Vol 64 (1) ◽  
pp. 70-72 ◽  
Author(s):  
Rohit Sharma ◽  
Yujuan Wang ◽  
Pei Zhou ◽  
Richard A. Steinman ◽  
Qingde Wang
Keyword(s):  
Rna Editing ◽  
Essential Role ◽  
Mouse Skin ◽  
Editing Enzyme
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