Title | AU-Rich Element RNA Binding Proteins: At the Crossroads of Post-Transcriptional Regulation and Genome Integrity. |
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Type | Journal article |
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Authors | Sidali, A., Teotia, Varsha, Solaiman, Nadeen Shaikh, Bashir, Nahida, Kanagaraj, Radhakrishnan, Murphy, J. and Surendranath, K. |
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Abstract | Genome integrity must be tightly preserved to ensure cellular survival and to deter the genesis of disease. Endogenous and exogenous stressors that impose threats to genomic stability through DNA damage are counteracted by a tightly regulated DNA damage response (DDR). RNA binding proteins (RBPs) are emerging as regulators and mediators of diverse biological processes. Specifically, RBPs that bind to adenine uridine (AU)-rich elements (AREs) in the 3' untranslated region (UTR) of mRNAs (AU-RBPs) have emerged as key players in regulating the DDR and preserving genome integrity. Here we review eight established AU-RBPs (AUF1, HuR, KHSRP, TIA-1, TIAR, ZFP36, ZFP36L1, ZFP36L2) and their ability to maintain genome integrity through various interactions. We have reviewed canonical roles of AU-RBPs in regulating the fate of mRNA transcripts encoding DDR genes at multiple post-transcriptional levels. We have also attempted to shed light on non-canonical roles of AU-RBPs exploring their post-translational modifications (PTMs) and sub-cellular localization in response to genotoxic stresses by various factors involved in DDR and genome maintenance. Dysfunctional AU-RBPs have been increasingly found to be associated with many human cancers. Further understanding of the roles of AU-RBP in maintaining genomic integrity may uncover novel therapeutic strategies for cancer. |
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Keywords | Adenine-Uridine rich element |
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| oncogenes |
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| DNA damage response |
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| cancer |
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| post-transcriptional regulation |
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| tumour suppressors |
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| replication stress |
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| RNA binding proteins |
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| genome stability |
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Article number | 96 |
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Journal | International Journal of Molecular Sciences |
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Journal citation | 23 (1) |
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ISSN | 1422-0067 |
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Year | 2021 |
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Publisher | MDPI |
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Publisher's version | License CC BY 4.0 File Access Level Open (open metadata and files) |
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Digital Object Identifier (DOI) | https://doi.org/10.3390/ijms23010096 |
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PubMed ID | 35008519 |
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Web address (URL) | https://doi.org/10.3390/ijms23010096 |
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Publication dates |
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Published | 22 Dec 2021 |
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Published | 22 Dec 2021 |
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Published online | 22 Dec 2021 |
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Project | PGTaSFA\100027 |
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Funder | Children with Cancer UK |
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