Targeted RNA editing: novel tools to study post-transcriptional regulation

Xu, Wei; Biswas, Jeetayu; Singer, Robert H.; Rosbash, Michael

doi:10.1016/j.molcel.2021.10.010

Cited by 20 publications

(17 citation statements)

References 136 publications

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“…The APOBEC expression burden may also be applied as an indicator for the risk of developing cancerous disease in the future. Moreover, APOBECs are promising base editing tools and probably have therapeutic implications in gene therapy [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

Aberrant APOBEC3C expression induces characteristic genomic instability in pancreatic ductal adenocarcinoma

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is a well-known lethal and heterogeneous disease. Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like (APOBEC) is an important mutagenic driver that has seldom been investigated in PDAC. Therefore, this study investigated the significance of APOBEC3C in PDAC. First, cytosine deamination-associated mutation signatures were identified in the PDAC cohorts from TCGA and Fudan University Shanghai Cancer Center (FUSCC) datasets, and C > X-enriched kataegis regions were identified in the FUSCC cohort (12 to 27 counts per sample). Patients were stratified according to APOBEC3C expression, and high APOBEC3C expression was found to correlate with a higher motif enrichment score of 5’-CC-3’ and an elevated kataegis count within PCSK5 and NES genes. Second, we compared APOBEC expression in PDAC and normal pancreatic tissues and found that APOBEC3C was substantially upregulated in PDAC. APOBEC3C-overexpressing cell lines were generated to substantiate the effects of APOBEC3C on PDAC genome, including alterations in single-nucleotide variant (SNV) classes (higher proportion of C > T conversions) and the formation of kataegis regions (newly occurring kataegis regions detected in ACHE and MUC6 genes). Three different PDAC cohorts (FUSCC, TCGA, and QCMG) were analysed to evaluate the prognostic value of APOBEC3C, and APOBEC3C overexpression predicted shorter survival. Finally, the APOBEC3C overexpression correalted with the PDAC tumour microenvironment (TME) remodelling, APOBEC3C expression was associated with the invasion of CD4 + T lymphocytes and CD8 + T lymphocytes (cytotoxic T lymphocytes, CTLs), indicating enhanced immune activity and validating the practicality of APOBEC3C for guiding immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Aberrant APOBEC3C expression induces characteristic genomic instability in pancreatic ductal adenocarcinoma

et al. 2022

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“…Recent studies indicated that lncRNAs partner with RBPs to enable certain functions [ 6 ]. YBX1, a multi-functional RNA-binding protein, has demonstrated that it can interact with LncRNAs and affect angiogenesis [ 18 ].…”

Section: Resultsmentioning

confidence: 99%

“…Their roles have been recently appreciated in cancer diseases [ 5 ]. Recent research revealed that RNA-binding proteins (RBPs) and miRNAs control the post-transcription process, including RNA decay and stability, and regulate gene expression [ 6 ]. The roles of lncRNAs remain to be further investigated.…”

Section: Introductionmentioning

confidence: 99%

MEG3 sponges miRNA-376a and YBX1 to regulate angiogenesis in ovarian cancer endothelial cells

Zhang²,

Zhao³

et al. 2023

Heliyon

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“…Furthermore, TRIBE-STAMP could be coupled with long-read sequencing to identify RNA molecules co-bound by RBPs that recognize distinct transcript regions separated by large distances, such as the 5’UTR and 3’UTR. In theory, TRIBE-STAMP could also be used in conjunction with PUP-2 or APEX2 labeling to identify the targets of more than two RBPs at once (Lapointe et al 2015; Fazal et al 2019; Padron et al 2019; Xu et al 2022). Thus, the TRIBE-STAMP method provides a versatile approach for investigating RNA:protein interactions in cells and enables single-molecule binding information for multiple RBPs at once, therefore overcoming the limitations of many current protein-centric methods which only examine single RBPs in isolation.…”

Section: Discussionmentioning

confidence: 99%

Single-molecule identification of the target RNAs of different RNA binding proteins simultaneously in cells

Flamand

Tamming

et al. 2022

Preprint

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RNA-binding proteins (RBPs) regulate nearly every aspect of mRNA processing and are important regulators of gene expression in cells. However, current methods for transcriptome-wide identification of RBP targets are limited since they examine only a single RBP at a time and since they do not provide information on the individual RNA molecules that are bound by a given RBP. Here, we overcome these limitations by developing TRIBE-STAMP, an approach for single-molecule detection of the target RNAs of two RNA binding proteins simultaneously in cells. We apply TRIBE-STAMP to the cytoplasmic m6A reader proteins YTHDF1, 2, and 3 and discover that individual mRNA molecules can be bound by more than one YTHDF protein throughout their lifetime, providing new insights into the function of YTHDF proteins in cells. TRIBE-STAMP is a highly versatile approach that enables single-molecule analysis of the targets of RBP pairs simultaneously in the same cells.

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Targeted RNA editing: novel tools to study post-transcriptional regulation

Cited by 20 publications

References 136 publications

Aberrant APOBEC3C expression induces characteristic genomic instability in pancreatic ductal adenocarcinoma

Aberrant APOBEC3C expression induces characteristic genomic instability in pancreatic ductal adenocarcinoma

MEG3 sponges miRNA-376a and YBX1 to regulate angiogenesis in ovarian cancer endothelial cells

Single-molecule identification of the target RNAs of different RNA binding proteins simultaneously in cells

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