RNA Recognition Motif 2 Directs the Recruitment of SF2/ASF to Nuclear Stress Bodies
Overview
Authors
Affiliations
Heat shock induces the transcriptional activation of large heterochromatic regions of the human genome composed of arrays of satellite III DNA repeats. A number of RNA-processing factors, among them splicing factor SF2/ASF, associate with these transcription factors giving rise to nuclear stress bodies (nSBs). Here, we show that the recruitment of SF2/ASF to these structures is mediated by its second RNA recognition motif. Amino acid substitutions in the first alpha-helix of this domain, but not in the beta-strand regions, abrogate the association with nSBs. The same mutations drastically affect the in vivo activity of SF2/ASF in the alternative splicing of adenoviral E1A transcripts. Sequence analysis identifies four putative high-affinity binding sites for SF2/ASF in the transcribed strand of the satellite III DNA. We have verified by gel mobility shift assays that the second RNA-binding domain of SF2/ASF binds at least one of these sites. Our analysis suggests that the recruitment of SF2/ASF to nSBs is mediated by a direct interaction with satellite III transcripts and points to the second RNA-binding domain of the protein as the major determinant of this interaction.
Answering the Cell Stress Call: Satellite Non-Coding Transcription as a Response Mechanism.
Fonseca-Carvalho M, Verissimo G, Lopes M, Ferreira D, Louzada S, Chaves R Biomolecules. 2024; 14(1).
PMID: 38254724 PMC: 10813801. DOI: 10.3390/biom14010124.
Jeon P, Ham H, Park S, Lee J Cells. 2022; 11(13).
PMID: 35805146 PMC: 9265587. DOI: 10.3390/cells11132063.
Mechanistic and Therapeutic Insights into Ataxic Disorders with Pentanucleotide Expansions.
Zhang N, Ashizawa T Cells. 2022; 11(9).
PMID: 35563872 PMC: 9099484. DOI: 10.3390/cells11091567.
Vourch C, Dufour S, Timcheva K, Seigneurin-Berny D, Verdel A Genes (Basel). 2022; 13(4).
PMID: 35456403 PMC: 9032817. DOI: 10.3390/genes13040597.
Porokhovnik L, Veiko N, Ershova E, Kostyuk S Genes (Basel). 2021; 12(10).
PMID: 34680920 PMC: 8535310. DOI: 10.3390/genes12101524.