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  2. Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks

Genome-wide RNA structure changes during human neurogenesis modulate gene regulatory networks

  • Mol Cell. 2021 Dec 2;81(23):4942-4953.e8. doi: 10.1016/j.molcel.2021.09.027.
Jiaxu Wang 1 Tong Zhang 1 Zhang Yu 1 Wen Ting Tan 1 Ming Wen 1 Yang Shen 1 Finnlay R P Lambert 2 Roland G Huber 3 Yue Wan 4
Affiliations

Affiliations

  • 1 Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore.
  • 2 Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore; Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, UK.
  • 3 Bioinformatics Institute, A(∗)STAR, Singapore 138671, Singapore.
  • 4 Stem Cell and Regenerative Biology, Genome Institute of Singapore, A(∗)STAR, Singapore 138672, Singapore; Department of Biochemistry, National University of Singapore, Singapore 117596, Singapore. Electronic address: wany@gis.a-star.edu.sg.
Abstract

The distribution, dynamics, and function of RNA structures in human development are under-explored. Here, we systematically assayed RNA structural dynamics and their relationship with gene expression, translation, and decay during human neurogenesis. We observed that the human ESC transcriptome is globally more structurally accessible than differentiated cells and undergoes extensive RNA structure changes, particularly in the 3' UTR. Additionally, RNA structure changes during differentiation are associated with translation and decay. We observed that RBP and miRNA binding is associated with RNA structural changes during early neuronal differentiation, and splicing is associated during later neuronal differentiation. Furthermore, our analysis suggests that RBPs are major factors in structure remodeling and co-regulate additional RBPs and miRNAs through structure. We demonstrated an example of this by showing that PUM2-induced structure changes on LIN28A enable miR-30 binding. This study deepens our understanding of the widespread and complex role of RNA-based gene regulation during human development.

Keywords

RNA binding proteins; RNA modification; RNA structure; co-regulation; high-throughput sequencing; human neurogenesis; miRNAs; splicing; systems biology.

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