Downregulation of Gene Expression by Alpha Satellite Transcripts

Ljubić, Sven; Matulić, Maja; Đermić, Damir; Feliciello, Maria Chiara; Procino, Alfredo; Passaro, Francesco; Ugarković, Đurđica; Feliciello, Isidoro (2025) Downregulation of Gene Expression by Alpha Satellite Transcripts. International Journal of Molecular Sciences, 26 (22). ISSN 1422-0067

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Abstract

Satellite DNAs are highly abundant sequences that build functional centromeres and pericentromeric heterochromatin in many eukaryotes. Apart from this structural role, their involvement in gene expression modulation has been demonstrated, although a detailed understanding of the molecular mechanisms is still lacking. Here, using the major human alpha satellite as a model system, we investigate the role of satellite transcripts in gene expression regulation. We generated cell lines with forced, exogenous overexpression of alpha satellite RNA and followed the expression levels of genes containing alpha satellite repeats within introns. Our results reveal a positive correlation between exogenous alpha satellite expression and the downregulation of alpha-associated genes, strongly suggesting that alpha satellite RNA affects their transcription. Notably, the elevated levels of exogenous alpha satellite RNA did not affect histone modifications characteristic of pericentromeric heterochromatin (e.g., H3K9me3 or H3K18Ac) or euchromatin (e.g., H3K4me2) at intronic alpha satellite loci. We propose that alpha satellite RNA directly interacts with homologous DNA at dispersed intronic satellite loci by forming RNA-DNA hybrid structures, which may affect chromatin structure and transcriptional activity. The results demonstrate that alpha satellite RNA is not only involved in centromere and heterochromatin assembly but, as shown here for the first time, also plays a role in modulating the expression of alpha-associated genes.

Item Type:	Article
Uncontrolled Keywords:	satellite DNA; transcription; gene expression; RNA-DNA hybrid; heterochromatin; histone modifications; alpha satellite DNA
Subjects:	NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology
Divisions:	Division of Molecular Biology
Projects:	Project title Project leader Project code Project type Alfa satelitska DNA u evoluciji mreža genske modulacije-AlphaSatGenNet Đurđica Ugarković; Dušan Kordiš; Jure Skejić; Antonio Sermek IP-2019-04-6915 HRZZ
Depositing User:	Lorena Palameta
Date Deposited:	26 Nov 2025 15:03
URI:	http://fulir.irb.hr/id/eprint/10248
DOI:	10.3390/ijms262211204

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