DNA-Damage Response RNA-Binding Proteins (DDRBPs): Perspectives from a New Class of Proteins and Their RNA Targets

2017 ◽  
Vol 429 (21) ◽  
pp. 3139-3145 ◽  
Author(s):  
Martin Dutertre ◽  
Stéphan Vagner
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
New Class ◽  
Rna Targets ◽  
Damage Response

scholarly journals The Role of Small Noncoding RNA in DNA Double-Strand Break Repair

2020 ◽  
Vol 21 (21) ◽  
pp. 8039
Author(s):  
Iwona Rzeszutek ◽  
Gabriela Betlej
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Noncoding Rna ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Strand Break ◽  
Double Strand Break ◽  
Wide Range ◽  
Damage Response

DNA damage is a common phenomenon promoted through a variety of exogenous and endogenous factors. The DNA damage response (DDR) pathway involves a wide range of proteins, and as was indicated, small noncoding RNAs (sncRNAs). These are double-strand break-induced RNAs (diRNAs) and DNA damage response small RNA (DDRNA). Moreover, RNA binding proteins (RBPs) and RNA modifications have also been identified to modulate diRNA and DDRNA function in the DDR process. Several theories have been formulated regarding the synthesis and function of these sncRNAs during DNA repair; nevertheless, these pathways’ molecular details remain unclear. Here, we review the current knowledge regarding the mechanisms of diRNA and DDRNA biosynthesis and discuss the role of sncRNAs in maintaining genome stability.

scholarly journals p53 mRNA Metabolism Links with the DNA Damage Response

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1446
Author(s):  
Sivakumar Vadivel Vadivel Gnanasundram ◽  
Ondrej Bonczek ◽  
Lixiao Wang ◽  
Sa Chen ◽  
Robin Fahraeus
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Repair ◽  
Dna Damage Response ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Genotoxic Stress ◽  
Repair Processes ◽  
Damage Response ◽  
P53 Mrna

Human cells are subjected to continuous challenges by different genotoxic stress attacks. DNA damage leads to erroneous mutations, which can alter the function of oncogenes or tumor suppressors, resulting in cancer development. To circumvent this, cells activate the DNA damage response (DDR), which mainly involves cell cycle regulation and DNA repair processes. The tumor suppressor p53 plays a pivotal role in the DDR by halting the cell cycle and facilitating the DNA repair processes. Various pathways and factors participating in the detection and repair of DNA have been described, including scores of RNA-binding proteins (RBPs) and RNAs. It has become increasingly clear that p53’s role is multitasking, and p53 mRNA regulation plays a prominent part in the DDR. This review is aimed at covering the p53 RNA metabolism linked to the DDR and highlights the recent findings.

scholarly journals MBNL2 Regulates DNA Damage Response via Stabilizing p21

2021 ◽  
Vol 22 (2) ◽  
pp. 783
Author(s):  
Jin Cai ◽  
Ningchao Wang ◽  
Guanglan Lin ◽  
Haowei Zhang ◽  
Weidong Xie ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Dna Damage ◽  
Tumor Cell ◽  
Dna Damage Response ◽  
Rna Binding ◽  
Kinase Inhibitor ◽  
Rna Binding Proteins ◽  
Human Cancer ◽  
Tumor Cell Proliferation ◽  
Damage Response

RNA-binding proteins are frequently dysregulated in human cancer and able to modulate tumor cell proliferation as well as tumor metastasis through post-transcriptional regulation on target genes. Abnormal DNA damage response and repair mechanism are closely related to genome instability and cell transformation. Here, we explore the function of the RNA-binding protein muscleblind-like splicing regulator 2 (MBNL2) on tumor cell proliferation and DNA damage response. Transcriptome and gene expression analysis show that the PI3K/AKT pathway is enriched in MBNL2-depleted cells, and the expression of cyclin-dependent kinase inhibitor 1A (p21CDKN1A) is significantly affected after MBNL2 depletion. MBNL2 modulates the mRNA and protein levels of p21, which is independent of its canonical transcription factor p53. Moreover, depletion of MBNL2 increases the phosphorylation levels of checkpoint kinase 1 (Chk1) serine 345 (S345) and DNA damage response, and the effect of MBNL2 on DNA damage response is p21-dependent. MBNL2 would further alter tumor cell fate after DNA damage, MBNL2 knockdown inhibiting DNA damage repair and DNA damage-induced senescence, but promoting DNA damage-induced apoptosis.

scholarly journals SSMART: Sequence-structure motif identification for RNA-binding proteins

2018 ◽  
Author(s):  
Alina Munteanu ◽  
Neelanjan Mukherjee ◽  
Uwe Ohler
Keyword(s):  
Binding Sites ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Sequence Motif ◽  
Primary Sequence ◽  
Sequence Structure ◽  
Rna Targets

AbstractMotivationRNA-binding proteins (RBPs) regulate every aspect of RNA metabolism and function. There are hundreds of RBPs encoded in the eukaryotic genomes, and each recognize its RNA targets through a specific mixture of RNA sequence and structure properties. For most RBPs, however, only a primary sequence motif has been determined, while the structure of the binding sites is uncharacterized.ResultsWe developed SSMART, an RNA motif finder that simultaneously models the primary sequence and the structural properties of the RNA targets sites. The sequence-structure motifs are represented as consensus strings over a degenerate alphabet, extending the IUPAC codes for nucleotides to account for secondary structure preferences. Evaluation on synthetic data showed that SSMART is able to recover both sequence and structure motifs implanted into 3‘UTR-like sequences, for various degrees of structured/unstructured binding sites. In addition, we successfully used SSMART on high-throughput in vivo and in vitro data, showing that we not only recover the known sequence motif, but also gain insight into the structural preferences of the RBP.AvailabilitySSMART is freely available at https://ohlerlab.mdc-berlin.de/software/SSMART_137/[email protected]

scholarly journals ATM regulates a DNA damage response posttranscriptional RNA operon in lymphocytes

Blood ◽  
2011 ◽  
Vol 117 (8) ◽  
pp. 2441-2450 ◽  
Author(s):  
Krystyna Mazan-Mamczarz ◽  
Patrick R. Hagner ◽  
Yongqing Zhang ◽  
Bojie Dai ◽  
Elin Lehrmann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Rna Binding ◽  
Critical Role ◽  
Cell Cycle Checkpoints ◽  
Dependent Manner ◽  
Damage Response ◽  
Multiple Cell

Abstract Maintenance of genomic stability depends on the DNA damage response, a biologic barrier in early stages of cancer development. Failure of this response results in genomic instability and high predisposition toward lymphoma, as seen in patients with ataxia-telangiectasia mutated (ATM) dysfunction. ATM activates multiple cell-cycle checkpoints and DNA repair after DNA damage, but its influence on posttranscriptional gene expression has not been examined on a global level. We show that ionizing radiation modulates the dynamic association of the RNA-binding protein HuR with target mRNAs in an ATM-dependent manner, potentially coordinating the genotoxic response as an RNA operon. Pharmacologic ATM inhibition and use of ATM-null cells revealed a critical role for ATM in this process. Numerous mRNAs encoding cancer-related proteins were differentially associated with HuR depending on the functional state of ATM, in turn affecting expression of encoded proteins. The findings presented here reveal a previously unidentified role of ATM in controlling gene expression posttranscriptionally. Dysregulation of this DNA damage response RNA operon is probably relevant to lymphoma development in ataxia-telangiectasia persons. These novel RNA regulatory modules and genetic networks provide critical insight into the function of ATM in oncogenesis.

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