Novel domains in the hnRNP G/RBMX protein with distinct roles in RNA binding and targeting nascent transcripts

Kanhoush, Rasha; Beenders, Brent; Perrin, Caroline; Moreau, Jacques; Bellini, Michel; Penrad-Mobayed, May

doi:10.4161/nucl.1.1.10857

Cited by 33 publications

(39 citation statements)

References 48 publications

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“…Also, very little is known about the RBP function of RBMX, which was previously better known as a transcription factor. However, one recent study has found RBMX's preference for hairpin stem-loop structures in RNAs (Kanhoush et al 2009). …”

Section: Discussionmentioning

confidence: 97%

The regulatory epicenter of miRNAs

2011

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miRNAs are small non-coding RNAs with average length of ~21 bp. miRNA formation seems to be dependent upon multiple factors besides Drosha and Dicer, in a tissue/stage-specific manner, with interplay of several specific binding factors. In the present study, we have investigated transcription factor binding sites in and around the genomic sequences of precursor miRNAs and RNA-binding protein (RBP) sites in miRNA precursor sequences, analysed and tested in comprehensive manner. Here, we report that miRNA precursor regions are positionally enriched for binding of transcription factors as well as RBPs around the 3' end of mature miRNA region in 5' arm. The pattern and distribution of such regulatory sites appears to be a characteristic of precursor miRNA sequences when compared with non-miRNA sequences as negative dataset and tested statistically.When compared with 1 kb upstreamregions, a sudden sharp peak for binding sites arises in the enriched zone near the mature miRNA region. An expression-data-based correlation analysis was performed between such miRNAs and their corresponding transcription factors and RBPs for this region. Some specific groups of binding factors and associated miRNAs were identified. We also identified some of the overrepresented transcription factors and associated miRNAs with high expression correlation values which could be useful in cancer-related studies. The highly correlated groups were found to host experimentally validated composite regulatory modules, in which Lmo2-GATA1 appeared as the predominant one. For many of RBP-miRNAs associations, coexpression similarity was also evident among the associated miRNA common to given RBPs, supporting the Regulon model, suggesting a common role and common control of these miRNAs by the associated RBPs. Based on our findings, we propose that the observed characteristic distribution of regulatory sites in precursor miRNA sequence regions could be critical inmiRNA transcription, processing, stability and formation and are important for therapeutic studies. Our findings also support the recently proposed theory of self-sufficient mode of transcription by miRNAs, which states that miRNA transcription can be carried out in host-independent mode too.

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Section: Discussionmentioning

confidence: 97%

The regulatory epicenter of miRNAs

2011

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“…Although our down-regulated miRNAs, miR-133b and miR-454, are certainly not pregnancy specific, their down-regulation during pregnancy allows for an increase in the translation of numerous mRNAs, including X-linked RNA binding motif protein (RBMX) which is implicated in regulation of gene transcription and alternative splicing, as well as repairing double-stranded DNA breaks [28, 29] and DEAD (Asp-Glu-Ala-Asp) box helicase 6 (DDX6) which maintains adult progenitor cell function [30]. …”

Section: Discussionmentioning

confidence: 99%

Evaluation of circulating miRNAs during late pregnancy in the mare

et al. 2017

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MicroRNAs (miRNAs) are small, non-coding RNAs which are produced throughout the body. Individual tissues tend to have a specific expression profile and excrete many of these miRNAs into circulation. These circulating miRNAs may be diagnostically valuable biomarkers for assessing the presence of disease while minimizing invasive testing. In women, numerous circulating miRNAs have been identified which change significantly during pregnancy-related complications (e.g. chorioamnionitis, eclampsia, recurrent pregnancy loss); however, no prior work has been done in this area in the horse. To identify pregnancy-specific miRNAs, we collected serial whole blood samples in pregnant mares at 8, 9, 10 m of gestation and post-partum, as well as from non-pregnant (diestrous) mares. In total, we evaluated a panel of 178 miRNAs using qPCR, eventually identifying five miRNAs of interest. One miRNA (miR-374b) was differentially regulated through late gestation and four miRNAs (miR-454, miR-133b, miR-486-5p and miR-204b) were differentially regulated between the pregnant and non-pregnant samples. We were able to identify putative targets for the differentially regulated miRNAs using two separate target prediction programs, miRDB and Ingenuity Pathway Analysis. The targets for the miRNAs differentially regulated during pregnancy were predicted to be involved in signaling pathways such as the STAT3 pathway and PI3/AKT signaling pathway, as well as more endocrine-based pathways, including the GnRH, prolactin and insulin signaling pathways. In summary, this study provides novel information about the changes occurring in circulating miRNAs during normal pregnancy, as well as attempting to predict the biological effects induced by these miRNAs.

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“…The protein has been reported to regulate tissue-specific gene transcription and alternative splicing of several pre-mRNAs (54,55). As none of the citrullination sites is located in the N-and C-terminal RNA-binding regions, citrullination of RBMX might not disturb its RNA-binding ability but potentially affect the structural stability or cellular localization of the protein because two of the citrullination sites, R223 and R232, are localized in a region essential for the association with nascent RNA polymerase II (RNAPII) and nuclear localization (55). Another example is TATA-binding protein-associated factor 2N (TAF15) which was identified in 7 tissues with 6 citrullination sites.…”

Section: The Landscape Of Protein Citrullination Of Human Tissuesmentioning

confidence: 99%

Mining the Human Tissue Proteome for Protein Citrullination

Lee

Wang

Wilhelm

et al. 2018

Molecular & Cellular Proteomics

175

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SummaryCitrullination is a post-translational modification of arginine catalyzed by five peptidylarginine deiminases (PADs) in humans. The loss of a positive charge may cause structural or functional alterations and while the modification has been linked to several diseases including rheumatoid arthritis and cancer, its physiological or pathophysiological roles remain largely unclear. In part this is owing to limitations in available methodology able to robustly enrich, detect and localize the modification. As a result, only few citrullination sites have been identified on human proteins with high confidence. In this study, we mined data from mass spectrometry-based deep proteomic profiling of 30 human tissues to identify citrullination sites on endogenous proteins. Database searching of ~70 million tandem mass spectra yielded ~13,000 candidate spectra which were further triaged by spectrum quality metrics and the detection of the specific neutral loss of isocyanic acid from citrullinated peptides to reduce false positives. Because citrullination is easily confused with deamidation, we synthetized ~2,200 citrullinated and 1,300 deamidated peptides to build a library of reference spectra. This led to the validation of 375 citrullination sites on 209 human proteins. Further analysis showed that >80% of the identified modifications sites were new and for 56% of the proteins, citrullination was detected for the first time. Sequence motif analysis revealed a strong preference for Asp and Gly, residues around the citrullination site. Interestingly, while the modification was detected in 26 human tissues with the highest levels found in brain and lung, citrullination levels did not correlate well with protein expression of the PAD enzymes.Even though the current work represents the largest survey of protein citrullination to date, the modification was mostly detected on high abundant proteins arguing that the development of specific enrichment methods would be required in order to study the full extent of cellular protein citrullination.

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Novel domains in the hnRNP G/RBMX protein with distinct roles in RNA binding and targeting nascent transcripts

Cited by 33 publications

References 48 publications

The regulatory epicenter of miRNAs

The regulatory epicenter of miRNAs

Evaluation of circulating miRNAs during late pregnancy in the mare

Mining the Human Tissue Proteome for Protein Citrullination

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