Analysis of RNA binding properties of human Ku protein reveals its interactions with 7SK snRNA and protein components of 7SK snRNP complex

Shadrina, Olga; Garanina, Irina; Korolev, S. P.; Zatsepin, Timofei S.; Assche, Jeanne Van; Daouad, Fadoua; Wallet, Clémentine; Rohr, Olivier; Gottikh, Marina

doi:10.1016/j.biochi.2020.02.016

Cited by 11 publications

(11 citation statements)

References 90 publications

(118 reference statements)

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“…Additionally, we observed BCL11b is associated with proteins involved in DNA repair and cellular response to stimuli (such as BRCA2, MCMs, PARP1, and SMCs proteins). In agreement to our results, BCL11b was previously shown to interact with Ku70 and Ku80 proteins, which have an important role in the non-homologous end-joining DNA repair pathway (Shadrina et al, 2020).…”

Section: Resultssupporting

confidence: 93%

“…In agreement to our results, BCL11b was previously shown to interact with Ku70 and Ku80 proteins, which have an important role in the non-homologous end-joining DNA repair pathway (Shadrina et al, 2020).…”

Section: Bcl11b Interacts With Proteins Dedicated To Genetic and Epigsupporting

confidence: 93%

“…After statistical analysis, we identified 629 BCL11b protein partners (supplementary method file S1 and supplementary dataset S1). Among the interacting proteins, we can confirm the previously described interactions between BCL11b and the P-TEFb complex (including CDK9 and CycT1) (Cherrier et al, 2013), HDACs (Marban et al, 2007), HMGA1 (Eilebrecht et al, 2014), HP1 proteins (Rohr et al, 2003), KU proteins (Shadrina et al, 2020), and DCAF1 (Forouzanfar et al, 2019) as a validation of our experimental approach ( Figure 1A).…”

Section: Protein Interactomics and Pathways Of Bcl11bsupporting

confidence: 85%

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BCL11b interacts with RNA and proteins involved in RNA processing and developmental diseases

Sobhy

Aït-Ammar

et al. 2020

Preprint

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Although BCL11b (B-cell lymphoma/leukemia 11B, CTIP2) is a well-known transcription repressor and tumor suppressor, its functions and cellular pathways are largely unknown. Here, we show that BCL11b interacts with RNA splicing/processing and nonsense-mediated decay (NMD) proteins, including FUS, SMN1, UPF1 and Drosha. Mass spectrometry analysis (LC-MS/MS) shows that BCL11b interacts with histones, polymerases, and chromatin remodeling (CHD, SWI/SNF, and topoisomerase) proteins. BCL11b-bound RNAs were UV cross-linked and sequenced (CLIP-seq) showing that BCL11b binds to coding and noncoding RNAs (ncRNAs). Surprisingly, RNA transcripts and proteins produced by the same genes like FUS, ESWR1, CHD and Tubulin, were found bound to BCL11b. Deeper analysis of the CLIP-seq data further suggested that BCL11b binds to nonsense mediated RNA decay and retained introns transcripts. Our study is the first genome-wide study of BCL11b-protein and BCL11b-RNA interactants. Our results suggest that the functions of BCL11b are not restricted to the regulation of gene transcription. BCL11b may also control physiologic and physiopathologic pathways by direct bindings to protein complexes, coding RNA and non-coding RNA.

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Section: Resultssupporting

confidence: 93%

Section: Bcl11b Interacts With Proteins Dedicated To Genetic and Epigsupporting

confidence: 93%

Section: Protein Interactomics and Pathways Of Bcl11bsupporting

confidence: 85%

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BCL11b interacts with RNA and proteins involved in RNA processing and developmental diseases

Sobhy

Aït-Ammar

et al. 2020

Preprint

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“…Studies focusing on autophosphorylation of DNA-PKcs have indicated that while DNA-PKcs PQR/PQR mice were healthy, DNA-PKcs 5A/5A and DNA-PKcs 3A/3A mice showed bone marrow failure [ 34 , 53 ]. The fact that Ku binds to both DNA and RNA [ 65 , 66 ], and that the Ku complex and DNA-PKcs localize in the nucleolus in the absence of DNA damage [ 67 ], suggests that DNA-PK may act in an RNA-dependent manner in the nucleolus. Indeed, an analysis using v-ABL kinase-transformed pro-B cell lines from DNA-PKcs kd/kd and DNA-PKcs 3A/3A mice revealed that translation is reduced in these cells [ 34 ].…”

Section: Effects Of Dna-pkcs On Development and Differentiation Determined By Comparing Knockout And Mutant Micementioning

confidence: 99%

Autophosphorylation and Self-Activation of DNA-Dependent Protein Kinase

Kurosawa

2021

Genes

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The DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase-related kinase family, phosphorylates serine and threonine residues of substrate proteins in the presence of the Ku complex and double-stranded DNA. Although it has been established that DNA-PKcs is involved in non-homologous end-joining, a DNA double-strand break repair pathway, the mechanisms underlying DNA-PKcs activation are not fully understood. Nevertheless, the findings of numerous in vitro and in vivo studies have indicated that DNA-PKcs contains two autophosphorylation clusters, PQR and ABCDE, as well as several autophosphorylation sites and conformational changes associated with autophosphorylation of DNA-PKcs are important for self-activation. Consistent with these features, an analysis of transgenic mice has shown that the phenotypes of DNA-PKcs autophosphorylation mutations are significantly different from those of DNA-PKcs kinase-dead mutations, thereby indicating the importance of DNA-PKcs autophosphorylation in differentiation and development. Furthermore, there has been notable progress in the high-resolution analysis of the conformation of DNA-PKcs, which has enabled us to gain a visual insight into the steps leading to DNA-PKcs activation. This review summarizes the current progress in the activation of DNA-PKcs, focusing in particular on autophosphorylation of this kinase.

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“…In particular, it is known that DNA-PK may phosphorylate the C-terminal domain of RNAP II [ 74 ], and, along with the Ku70/Ku80 heterodimer, DNA-PKcs may be precipitated from human cells together with the RNAP II holoenzyme [ 160 ]. It has also been shown that the Ku70/Ku80 heterodimer may interact with hairpin RNA involved in transcription performed by RNAP II, HIV-1 TAR PHK and 7SK PHK [ 159 , 161 , 162 ], whereas the catalytic subunit of DNA-PKcs forms a complex with HIV-1 Tat [ 163 ] and may phosphorylate it [ 164 ]. These various data indicate the possible involvement of the DNA-PK DNA repair complex in the regulation of transcription from the HIV-1 promoter.…”

Section: Dna-pk Targets In Hiv Replicationmentioning

confidence: 99%

Phosphorylation Targets of DNA-PK and Their Role in HIV-1 Replication

Anisenko

Kan

Shadrina

et al. 2020

Cells

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The DNA dependent protein kinase (DNA-PK) is a trimeric nuclear complex consisting of a large protein kinase and the Ku heterodimer. The kinase activity of DNA-PK is required for efficient repair of DNA double-strand breaks (DSB) by non-homologous end joining (NHEJ). We also showed that the kinase activity of DNA-PK is essential for post-integrational DNA repair in the case of HIV-1 infection. Besides, DNA-PK is known to participate in such cellular processes as protection of mammalian telomeres, transcription, and some others where the need for its phosphorylating activity is not clearly elucidated. We carried out a systematic search and analysis of DNA-PK targets described in the literature and identified 67 unique DNA-PK targets phosphorylated in response to various in vitro and/or in vivo stimuli. A functional enrichment analysis of DNA-PK targets and determination of protein–protein associations among them were performed. For 27 proteins from these 67 DNA-PK targets, their participation in the HIV-1 life cycle was demonstrated. This information may be useful for studying the functioning of DNA-PK in various cellular processes, as well as in various stages of HIV-1 replication.

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Analysis of RNA binding properties of human Ku protein reveals its interactions with 7SK snRNA and protein components of 7SK snRNP complex

Abstract: Analysis of RNA binding properties of human Ku protein reveals its interactions with 7SK snRNA and protein components of 7SK snRNP complex, Biochimie,

Cited by 11 publications

References 90 publications

BCL11b interacts with RNA and proteins involved in RNA processing and developmental diseases

BCL11b interacts with RNA and proteins involved in RNA processing and developmental diseases

Autophosphorylation and Self-Activation of DNA-Dependent Protein Kinase

Phosphorylation Targets of DNA-PK and Their Role in HIV-1 Replication

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