Gadd45a is an RNA binding protein and is localized in nuclear speckles
| Autor: | Christof Niehrs, Andrea I. Schäfer, Andriy V. Kubarenko, Alexander N.R. Weber, Yuliya A. Sytnikova |
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| Rok vydání: | 2010 |
| Předmět: |
Xenopus
Genetics and Genomics/Nuclear Structure and Function lcsh:Medicine RNA-dependent RNA polymerase Cell Cycle Proteins Biology Xenopus Proteins Biochemistry Cell Line DEAD-box RNA Helicases 03 medical and health sciences 0302 clinical medicine Transcription (biology) Animals Humans Point Mutation lcsh:Science Molecular Biology Molecular Biology/DNA Methylation 030304 developmental biology 0303 health sciences Multidisciplinary Serine-Arginine Splicing Factors lcsh:R Intron RNA Nuclear Proteins RNA-Binding Proteins DNA Methylation Non-coding RNA Molecular biology Cell Nucleus Structures Cell biology RNA silencing DNA demethylation Ribonucleoproteins Molecular Biology/Nucleolus and Nuclear Bodies lcsh:Q Molecular Biology/RNA-Protein Interactions 030217 neurology & neurosurgery Small nuclear RNA Protein Binding Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 6, Iss 1, p e14500 (2011) |
| ISSN: | 1932-6203 |
| Popis: | Background The Gadd45 proteins play important roles in growth control, maintenance of genomic stability, DNA repair, and apoptosis. Recently, Gadd45 proteins have also been implicated in epigenetic gene regulation by promoting active DNA demethylation. Gadd45 proteins have sequence homology with the L7Ae/L30e/S12e RNA binding superfamily of ribosomal proteins, which raises the question if they may interact directly with nucleic acids. Principal Findings Here we show that Gadd45a binds RNA but not single- or double stranded DNA or methylated DNA in vitro. Sucrose density gradient centrifugation experiments demonstrate that Gadd45a is present in high molecular weight particles, which are RNase sensitive. Gadd45a displays RNase-sensitive colocalization in nuclear speckles with the RNA helicase p68 and the RNA binding protein SC35. A K45A point mutation defective in RNA binding was still active in DNA demethylation. This suggests that RNA binding is not absolutely essential for demethylation of an artificial substrate. A point mutation at G39 impared RNA binding, nuclear speckle localization and DNA demethylation, emphasizing its relevance for Gadd45a function. Significance The results implicate RNA in Gadd45a function and suggest that Gadd45a is associated with a ribonucleoprotein particle. |
| Databáze: | OpenAIRE |
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