ArticleNPJ systems biology and applications2020
Genomic competition for noise reduction shaped evolutionary landscape of mir-4673.
Article in NPJ systems biology and applications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 7 citations in OpenAlex.
- Redox-Mediated Rewiring of Signalling Pathways: The Role of a Cellular Clock in Brain Health and Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Notch ankyrin domain: evolutionary rise of a thermodynamic sensor.Cell communication and signaling : CCS · 2022Article
- Programmed genomic instability regulates neural transdifferentiation of human brain microvascular pericytes.Genome biology · 2021Article
- Mechanosensitive pathways are regulated by mechanosensitive miRNA clusters in endothelial cells.Biophysical reviews · 2021Article
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3 authors at 1 institution in 1 country.
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Abstract
The genomic platform that informs evolution of microRNA cascades remains unknown. Here we capitalised on the recent evolutionary trajectory of hominin-specific miRNA-4673, encoded in intron 4 of notch-1, to uncover the identity of one such precursor genomic element and the selective forces acting upon it. The miRNA targets genes that regulate Wnt/β-catenin signalling cascade. Primary sequence of the microRNA and its target region in Wnt modulating genes evolved from homologous signatures mapped to homotypic cis-clusters recognised by TCF3/4 and TFAP2A/B/C families. Integration of homologous TFAP2A/B/C cis-clusters (short range inhibitor of β-catenin) into the transcriptional landscape of Wnt cascade genes can reduce noise in gene expression. Probabilistic adoption of miRNA secondary structure by one such cis-signature in notch-1 reflected selection for superhelical curvature symmetry of precursor DNA to localise a nucleosome that overlapped the latter cis-cluster. By replicating the cis-cluster signature, non-random interactions of the miRNA with key Wnt modulator genes expanded the transcriptional noise buffering capacity via a coherent feed-forward loop mechanism. In consequence, an autonomous transcriptional noise dampener (the cis-cluster/nucleosome) evolved into a post-transcriptional one (the miRNA). The findings suggest a latent potential for remodelling of transcriptional landscape by miRNAs that capitalise on non-random distribution of genomic cis-signatures.
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