Identification of deleterious non-synonymous single nucleotide polymorphisms in the mRNA decay activator ZFP36L2

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dc.contributor.authorAkçeşme, Betül
dc.contributor.authorHekimoğlu, Hilal
dc.contributor.authorChirasani, Venkat R.
dc.contributor.authorİş, Şeyma
dc.contributor.authorAtmaca, Habibe Nur
dc.contributor.authorWaldern, Justin M.
dc.contributor.authorRamos, Silvia B. V.
dc.date.accessioned2024-12-16T06:16:10Z
dc.date.available2024-12-16T06:16:10Z
dc.date.issued2024
dc.departmentTAÜ, Fen Fakültesi, Moleküler Biyoteknoloji Bölümüen_US
dc.description.abstractMore than 4,000 single nucleotide polymorphisms (SNP) variants have been identified in the human ZFP36L2 gene, however only a few have been studied in the context of protein function. The tandem zinc finger domain of ZFP36L2, an RNA binding protein, is the functional domain that binds to its target mRNAs. This protein/RNA interaction triggers mRNA degradation, controlling gene expression. We identified 32 non-synonymous SNPs (nsSNPs) in the tandem zinc finger domain of ZFP36L2 that could have possible deleterious impacts in humans. Using different bioinformatic strategies, we prioritized five among these 32 nsSNPs, namely rs375096815, rs1183688047, rs1214015428, rs1215671792 and rs920398592 to be validated. When we experimentally tested the functionality of these protein variants using gel shift assays, all five (Y154H, R160W, R184C, G204D, and C206F) resulted in a dramatic reduction in RNA binding compared to the WT protein. To understand the mechanistic effect of these variants on the protein/RNA interaction, we employed DUET, DynaMut and PyMOL to investigate structural changes in the protein. Additionally, we conducted Molecular Docking and Molecular Dynamics Simulations to fine tune the active behaviour of this biomolecular system at an atomic level. Our results propose atomic explanations for the impact of each of these five genetic variants identified.
dc.identifier.citationAkçeşme, B., Hekimoğlu, H., Chirasani, Venkat R., İş, Ş., Atmaca, Habibe N., Waldern, Justin M., Ramos, Silvia B. V. (2024). Identification of deleterious non-synonymous single nucleotide polymorphisms in the mRNA decay activator ZFP36L2. RNA Biology, 22 (1), 1-15.
dc.identifier.doi10.1080/15476286.2024.2437590
dc.identifier.endpage15en_US
dc.identifier.issue1en_US
dc.identifier.scopus2-s2.0-85212423940
dc.identifier.startpage1en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12846/1490
dc.identifier.volume22en_US
dc.identifier.wosWOS:001377002900001
dc.indekslendigikaynakWeb of Science
dc.language.isoen
dc.relation.ispartofRNA Biology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectZinc finger protein 36 like 2en_US
dc.subjectNon-synonymous single nucleotide polymorphisms (nsSNPs)en_US
dc.subjectDeleterious effecten_US
dc.subjectRNA binding proteinen_US
dc.subjectAdenine Uridine Rich Elements (AREs)en_US
dc.titleIdentification of deleterious non-synonymous single nucleotide polymorphisms in the mRNA decay activator ZFP36L2
dc.typeArticle

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