ADP-Ribosylation Post-Translational Modification: An Overview with a Focus on RNA Biology and New Pharmacological Perspectives

Manco, Giuseppe; Lacerra, Giuseppina; Porzio, Elena; Catara, Giuliana

doi:10.3390/biom12030443

Cited by 15 publications

(5 citation statements)

References 221 publications

(246 reference statements)

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“…PARylation of RBPs ultimately influences RNA processing and expression (59, 108). In particular, PARylation of splicing regulators is known to affect alternative splicing.…”

Section: Discussionmentioning

confidence: 99%

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

Breunig,

Lei,

Montalbano

et al. 2024

Preprint

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RNA binding proteins (RBPs) containing intrinsically disordered regions (IDRs) are present in diverse molecular complexes where they function as dynamic regulators. Their characteristics promote liquid-liquid phase separation (LLPS) and the formation of membraneless organelles such as stress granules and nucleoli. IDR-RBPs are particularly relevant in the nervous system and their dysfunction is associated with neurodegenerative diseases and brain tumor development. SERBP1 is a unique member of this group, being mostly disordered and lacking canonical RNA-binding domains. Using a proteomics approach followed by functional analysis, we defined SERBP1’s interactome. We uncovered novel SERBP1 roles in splicing, cell division, and ribosomal biogenesis and showed its participation in pathological stress granules and Tau aggregates in Alzheimer’s disease brains. SERBP1 preferentially interacts with other G-quadruplex (G4) binders, implicated in different stages of gene expression, suggesting that G4 binding is a critical component of SERBP1 function in different settings. Similarly, we identified important associations between SERBP1 and PARP1/polyADP-ribosylation (PARylation). SERBP1 interacts with PARP1 and its associated factors and influences PARylation. Moreover, protein complexes in which SERBP1 participates contain mostly PARylated proteins and PAR binders. Based on these results, we propose a feedback regulatory model in which SERBP1 influences PARP1 function and PARylation, while PARylation modulates SERBP1 functions and participation in regulatory complexes.

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“…PARylation of RBPs ultimately influences RNA processing and expression (59, 108). In particular, PARylation of splicing regulators is known to affect alternative splicing.…”

Section: Discussionmentioning

confidence: 99%

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

Breunig,

Lei,

Montalbano

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Certain PARP family enzymes exhibit poly-catalyzed enzymatic activity, whereas others are characterized by mono-catalyzed enzymatic activity (Table II) (65). PARPis competitively bind to the NAD + binding sites of the PARP1/2 enzymes and inhibit PARylation, improving the clinical benefits in BRCA mutant tumors (Table I).…”

Section: Role Of Parp In Synthetic Lethal Effects and Cell Deathmentioning

confidence: 99%

Roles of DNA damage repair and precise targeted therapy in renal cancer (Review)

Lai

et al. 2022

Oncol Rep

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The primary subtypes of renal cell carcinoma (RCC) include clear cell, papillary and chromophobe RCC. RCC occurs often due to loss of von Hippel-Lindau (VHL) and accumulation of lipids and glycogen, and RCC cells may exhibit sensitivity to the disruption of normal metabolism or homologous recombination gene defect. Although the application of molecular-targeted drugs (tyrosine kinase inhibitors) and immune checkpoint inhibitors has been recommended for the treatment of advanced RCC, more targets of DNA damage

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“…Based on the length, the ncRNAs can be arbitrarily defined as either long non-coding RNAs (lncRNAs, at least 200 nucleotides) or smaller non-coding RNAs such as transfer RNA, microRNA (miRNA) and piwi interacting RNAs ( 12 - 14 ). MiRNAs and lncRNAs participate in many immune response processes based on the modulation of the immune response genes ( 15 ). The hypothesis of competing endogenous RNA (ceRNA) revealed a new mechanism of RNA interaction.…”

Section: Introductionmentioning

confidence: 99%

A ferroptosis-related ceRNA network for investigating the molecular mechanisms and the treatment of neonatal hypoxic-ischemic encephalopathy

Lu,

Shen,

Mao

et al. 2024

Transl Pediatr

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Background Neonatal hypoxic-ischemic brain damage (HIBD) is a clinical syndrome causing brain injury in newborns with obscure etiology. Increasing evidence suggests that ferroptosis plays a role in HIBD. This study aimed to clarify the key ferroptosis-related genes (FRGs) of HIBD, construct a long non-coding RNA-microRNA-messenger RNA (lncRNA-miRNA-mRNA) network, and further investigate the pathogenesis of HIBD. Methods Gene expression data were downloaded from the Gene Expression Omnibus and FerrDb databases. The differentially expressed lncRNAs and FRGs were screened, and the related miRNAs and mRNAs were predicted. The obtained mRNA was intersected with the differentially expressed FRGs (DE-FRGs) to identify the key DE-FRGs. Cell-type Identification by Estimating Relative Subsets of RNA Transcripts method was applied to analyze the immune cell infiltration level and the relationship between key genes and immune cells. Results Gene differential expression analysis revealed that 1,178 lncRNAs, 207 miRNAs, and 647 mRNAs were differentially expressed in the blood of HIBD patients in comparison to healthy controls. The correlations of the lncRNAs, miRNAs, and mRNAs lead to the establishment of a competing endogenous RNA (ceRNA) network associated with ferroptosis in HIBD. Further validation using an external dataset and quantitative real-time polymerase chain reaction (PCR) analysis of brain tissues from hypoxic-ischemic encephalopathy rats confirmed the expression patterns of three key genes, including HMOX1, MYCN , and QSOX1 . Meanwhile, the three key genes were closely correlated with the infiltration of multiple immune cells and might affect the function of HIBD regulatory genes such as CPT2 and GCK . In addition, drug prediction suggested that four drugs, including cephaeline, emetine, mestranol, and sulmazole, might alleviate HIBD. Conclusions Our study established a ceRNA network, identified three key genes, and predicted four drugs that are associated with ferroptosis in HIBD, which provides new ideas for the investigation of the disease mechanisms and might facilitate the diagnosis and treatment of the disease.

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ADP-Ribosylation Post-Translational Modification: An Overview with a Focus on RNA Biology and New Pharmacological Perspectives

Cited by 15 publications

References 221 publications

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

SERBP1 interacts with PARP1 and is present in PARylation-dependent protein complexes regulating splicing, cell division, and ribosome biogenesis

Roles of DNA damage repair and precise targeted therapy in renal cancer (Review)

A ferroptosis-related ceRNA network for investigating the molecular mechanisms and the treatment of neonatal hypoxic-ischemic encephalopathy

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