ADAR-mediated messenger RNA Editing: Analysis at the proteome level

Author(s):  
A. A. Kliuchnikova ◽  
K. G. Kuznetsova ◽  
S. A. Moshkovskii
2016 ◽  
Vol 62 (5) ◽  
pp. 510-519 ◽  
Author(s):  
A.A. Kliuchnikova ◽  
K.G. Kuznetsova ◽  
S.A. Moshkovskii

Post-transcriptional RNA editing by RNA specific adenosine deaminases (ADAR) was discovered more than two decades ago. It provides additional regulation of animal and human transcriptome. In most cases, it occurs in nervous tissue, where, as a result of the reaction, adenosine is converted to inosine in particular sites of RNA. In case of messenger RNA, during translation, inosine is recognized as guanine leading to amino acid substitutions. Those substitutions are shown to affect substantially the function of proteins, e.g. subunits of the glutamate receptor. Nevertheless, most of the works on RNA editing use analysis of nucleic acids, even those which deal with a coding RNA. In this review, we propose the use of shotgun proteomics based on high resolution liquid chromatography and mass spectrometry for investigation of the effects of RNA editing at the protein level. Recently developed methods of big data processing allow combining the results of various omics techniques, being referred to as proteogenomics. The proposed proteogenomic approach for the analysis of RNA editing at the protein level will directly conduct a qualitative and quantitative analysis of protein edited sequences in the scale of whole proteome.


2013 ◽  
Vol 4 (1) ◽  
Author(s):  
Leila E. Rieder ◽  
Cynthia J. Staber ◽  
Barry Hoopengardner ◽  
Robert A. Reenan

1996 ◽  
Vol 24 (3) ◽  
pp. 478-486 ◽  
Author(s):  
G. R. Skuse ◽  
A. J. Cappione ◽  
M. Sowden ◽  
L. J. Metheny ◽  
H. C. Smith

2010 ◽  
Vol 27 (5-6) ◽  
pp. 149-157 ◽  
Author(s):  
HENRIK RING ◽  
HENRIK BOIJE ◽  
CHAMMIRAN DANIEL ◽  
JOHAN OHLSON ◽  
MARIE ÖHMAN ◽  
...  

AbstractAdenosine-to-inosine (A-to-I) RNA editing is a cotranscriptional or posttranscriptional gene regulatory mechanism that increases the diversity of the proteome in the nervous system. Recently, the transcript for GABA type A receptor subunit α3 was found to be subjected to RNA editing. The aim of this study was to determine if editing of the chicken α3 subunit transcript occurs in the retina and if the editing is temporally regulated during development. We also raised the question if editing of the α3 transcript was temporally associated with the suggested developmental shift from excitation to inhibition in the GABA system. The editing frequency was studied by using Sanger and Pyrosequencing, and to monitor the temporal aspects, we studied the messenger RNA expression of the GABAA receptor subunits and chloride pumps, known to be involved in the switch. The results showed that the chick α3 subunit was subjected to RNA editing, and its expression was restricted to cells in the inner nuclear and ganglion cell layer in the retina. The extent of editing increased during development (after embryonic days 8–9) concomitantly with an increase of expression of the chloride pump KCC2. Expression of several GABAA receptor subunits known to mediate synaptic GABA actions was upregulated at this time. We conclude that editing of the chick GABAA subunit α3 transcript in chick retina gives rise to an amino acid change that may be of importance in the switch from excitatory to inhibitory receptors.


1990 ◽  
Vol 46 (11-12) ◽  
pp. 1142-1148 ◽  
Author(s):  
R. Cattaneo

1999 ◽  
Vol 19 (4) ◽  
pp. 370-375 ◽  
Author(s):  
Kumiko Yamaguchi ◽  
Fuminori Yamaguchi ◽  
Osamu Miyamoto ◽  
Osamu Hatase ◽  
Masaaki Tokuda

The ischemic tolerance is known to show protective effects on the neurons and the restricted Ca2+ influx through Ca2+ channels might be involved. In α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor, ribonucleic acid (RNA) editing of the GluR2 subunit determines receptor desensitization and Ca2+ permeability. The authors investigated the effect of ischemic tolerance on the messenger RNA editing of Q/R and R/G sites of GluR2 subunit in hippocampus. It was found that the rate of RNA editing in Q/R site showed no change (100% edited), whereas that in R/G site decreased significantly (83.3% normal editing level to 60.4%) at day 3 (preconditioning period) and returned to normal level at day 14 (after preconditioning period). Further investigation revealed that the decrease of editing rate in ischemic tolerance resulted mainly from the decrease of editing in CA1 area.


2017 ◽  
Author(s):  
Ksenia G Kuznetsova ◽  
Anna A Kliuchnikova ◽  
Irina Y Ilina ◽  
Alexey L Chernobrovkin ◽  
Svetlana E Novikova ◽  
...  

Adenosine-to-inosine RNA editing is one of the most common types of RNA editing, a posttranscriptional modification made by special enzymes. We present a proteomic study on this phenomenon for Drosophila melanogaster. Three proteome data sets were used in the study: two taken from public repository and the third one obtained here. A customized protein sequence database was generated using results of genome-wide adenosine-to-inosine RNA studies and applied for identifying the edited proteins. The total number of 68 edited peptides belonging to 59 proteins was identified in all data sets. Eight of them being shared between the whole insect, head and brain proteomes. Seven edited sites belonging to synaptic vesicle and membrane trafficking proteins were selected for validation by orthogonal analysis by Multiple Reaction Monitoring. Five editing events in cpx, Syx1A, Cadps, CG4587 and EndoA were validated in fruit fly brain tissue at the proteome level using isotopically labeled standards. Ratios of unedited-to-edited proteoforms varied from 35:1 (Syx1A) to 1:2 (EndoA). Lys-137 to Glu editing of endophilin A may have functional consequences for its interaction to membrane. The work demonstrates the feasibility to identify the RNA editing event at the proteome level using shotgun proteomics and customized edited protein database.


Hepatology ◽  
2011 ◽  
Vol 53 (4) ◽  
pp. 1080-1089 ◽  
Author(s):  
Zong-Gen Peng ◽  
Zhi-Yun Zhao ◽  
Yan-Ping Li ◽  
Yu-Ping Wang ◽  
Lan-Hu Hao ◽  
...  

2016 ◽  
Vol 213 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Konstantin Licht ◽  
Michael F. Jantsch

Advances in next-generation sequencing and mass spectrometry have revealed widespread messenger RNA modifications and RNA editing, with dramatic effects on mammalian transcriptomes. Factors introducing, deleting, or interpreting specific modifications have been identified, and analogous with epigenetic terminology, have been designated “writers,” “erasers,” and “readers.” Such modifications in the transcriptome are referred to as epitranscriptomic changes and represent a fascinating new layer of gene expression regulation that has only recently been appreciated. Here, we outline how RNA editing and RNA modification can rapidly affect gene expression, making both processes as well suited to respond to cellular stress and to regulate the transcriptome during development or circadian periods.


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