Regulatory RNA binding proteins contribute to the transcriptome-wide splicing alterations in human cellular senescence

Dong, Qiongye; Wei, Lei; Zhang, Michael Q.; Wang, Xiaowo

doi:10.18632/aging.101485

Cited by 9 publications

(7 citation statements)

References 57 publications

(75 reference statements)

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“…Many lncRNAs can regulate the expression of downstream target genes by forming complexes with RNA‐binding proteins, then acts as an oncogene or a suppressor oncogene . In this study, we found that knockdown of MAPKAPK5‐AS1 in CRC cells could lead to changes in related downstream genes, including p15 , p21 , p27 , p57 , KLF2 , and Trail .…”

Section: Discussionmentioning

confidence: 64%

“…26 Therefore, the discovery of new CRC-related lncRNAs is of great significance for further understanding the molecular mechanisms of CRC progression and providing clinical therapeutic targets. In this study, we analyzed 2 sources Many lncRNAs can regulate the expression of downstream target genes by forming complexes with RNA-binding proteins, [27][28][29][30] then acts as an oncogene or a suppressor oncogene. [31][32][33][34][35] In this study, we found that knockdown of MAPKAPK5-AS1 in CRC cells could lead to changes in related downstream genes, including p15, p21, p27, p57, KLF2, and Trail.…”

Section: Discussionmentioning

confidence: 99%

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Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

et al. 2018

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Colorectal cancer (CRC) is the third most common malignancy in the world, and long noncoding RNA (lncRNA) plays a critical role in carcinogenesis. Here, we report a novel lncRNA, MAPKAPK5‐AS1, that acts as a critical oncogene in CRC. In addition, we attempted to explore the functions of MAPKAPK5‐AS1 on tumor progression in vitro and in vivo. Quantitative RT‐PCR was used to examine the expression of MAPKAPK5‐AS1 in CRC tissues and cells. Expression of MAPKAPK5‐AS1 was significantly upregulated in 50 CRC tissues, and increased expression of MAPKAPK5‐AS1 was found to be associated with greater tumor size and advanced pathological stage in CRC patients. Knockdown of MAPKAPK5‐AS1 significantly inhibited proliferation and caused apoptosis in CRC cells. We also found that p21 is a target of MAPKAPK5‐AS1. In addition, we are the first to report that MAPKAPK5‐AS1 plays a carcinogenic role in CRC. MAPKAPK5‐AS1 is a novel prognostic biomarker and a potential therapeutic candidate for CRC cancer.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

et al. 2018

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“…Altered senescence‐induced expression patterns of key SF families suggested a loss of AS regulation complexity with senescence (Holly et al, 2013). Moreover, numerous RNA‐binding proteins are downregulated upon senescence induction, and multiple differentially spliced events were shared between distinct pathways that induce senescence in human cells (Dong et al, 2018). Interestingly, many of the AS events occurred in genes associated with RNA splicing or the spliceosome itself.…”

Section: Hallmarks Of Aging and Splicingmentioning

confidence: 99%

“…Interestingly, many of the AS events occurred in genes associated with RNA splicing or the spliceosome itself. Combining differential gene expression data and binding motif data surrounding the differentially spliced genes, SFs SRSF1 , SRSF7 , QKI , RBFOX2 , PTBP1 , HNRNPK , HNRNPM , and HNRNPUL1 , were predicted as key regulators of senescence‐associated AS events (Dong et al, 2018). Similarly, senescent neuroblastoma cells were shown to suppress expression of SRSF7 (Kadota et al, 2020).…”

Section: Hallmarks Of Aging and Splicingmentioning

confidence: 99%

Splicing alterations in healthy aging and disease

Angarola¹,

Anczuków

2021

WIREs RNA

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Alternative RNA splicing is a key step in gene expression that allows generation of numerous messenger RNA transcripts encoding proteins of varied functions from the same gene. It is thus a rich source of proteomic and functional diversity. Alterations in alternative RNA splicing are observed both during healthy aging and in a number of human diseases, several of which display premature aging phenotypes or increased incidence with age. Age‐associated splicing alterations include differential splicing of genes associated with hallmarks of aging, as well as changes in the levels of core spliceosomal genes and regulatory splicing factors. Here, we review the current known links between alternative RNA splicing, its regulators, healthy biological aging, and diseases associated with aging or aging‐like phenotypes. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing

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“…Knowledge about the binding profiles of nucleic acid-binding proteins (NBPs) is a vital prerequisite to detecting potential NBP binding targets (i.e. RNAs and DNAs) in the cell, and understanding gene regulation and evolution ( Dong et al , 2018 ; Tak Leung et al , 2019 ; Yang et al , 2011 ). Currently, the binding profiles are mainly determined computationally ( Lambert et al , 2018 ; Pan et al , 2019 ) from high-throughput experimental data such as protein-binding microarray (PBM) ( Berger et al , 2006 ; Weirauch et al , 2014 ) or chromatin immunoprecipitation (ChIP)-seq ( Barski and Zhao, 2009 ; Park, 2009 ) for transcription factors (TFs), and RNAcompete assay ( Ray et al , 2009 , 2013 ) or crosslinking immunoprecipitation (CLIP) ( Konig et al , 2012 ; Wang et al , 2015 ) for RNA-binding proteins (RBPs).…”

Section: Introductionmentioning

confidence: 99%

ProbeRating: a recommender system to infer binding profiles for nucleic acid-binding proteins

Yang

Liu²,

2020

Bioinformatics

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Motivation The interaction between proteins and nucleic acids plays a crucial role in gene regulation and cell function. Determining the binding preferences of nucleic acid-binding proteins (NBPs), namely RNA-binding proteins (RBPs) and transcription factors (TFs), is the key to decipher the protein-nucleic acids interaction code. Today, available NBP binding data from in vivo or in vitro experiments are still limited, which leaves a large portion of NBPs uncovered. Unfortunately, existing computational methods that model the NBP binding preferences are mostly protein-specific: they need the experimental data for a specific protein in interest, and thus only focus on experimentally characterized NBPs. The binding preferences of experimentally unexplored NBPs remain largely unknown. Results Here, we introduce ProbeRating, a nucleic acid recommender system that utilizes techniques from deep learning and word embeddings of natural language processing. ProbeRating is developed to predict binding profiles for unexplored or poorly studied NBPs by exploiting their homologs NBPs which currently have available binding data. Requiring only sequence information as input, ProbeRating adapts FastText from Facebook AI Research to extract biological features. It then builds a neural network based recommender system. We evaluate the performance of ProbeRating on two different tasks: one for RBP and one for TF. As a result, ProbeRating outperforms previous methods on both tasks. The results show that ProbeRating can be a useful tool to study the binding mechanism for the many NBPs that lack direct experimental evidence. Availability The source code is freely available at < https://github.com/syang11/ProbeRating >. Supplementary information Supplementary data are available at Bioinformatics online.

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Regulatory RNA binding proteins contribute to the transcriptome-wide splicing alterations in human cellular senescence

Cited by 9 publications

References 57 publications

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

Long noncoding RNA MAPKAPK5-AS1 promotes colorectal cancer proliferation by partly silencing p21 expression

Splicing alterations in healthy aging and disease

ProbeRating: a recommender system to infer binding profiles for nucleic acid-binding proteins

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