Nuclear gene proximity and protein interactions shape transcript covariations in mammalian single cells.
Date
2020-10-28ICR Author
Author
Tarbier, M
Mackowiak, SD
Frade, J
Catuara-Solarz, S
Biryukova, I
Gelali, E
Menéndez, DB
Zapata, L
Ossowski, S
Bienko, M
Gallant, CJ
Friedländer, MR
Type
Journal Article
Metadata
Show full item recordAbstract
Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply a tailored experimental design that eliminates these confounders, and report thousands of intrinsically covarying gene pairs in mouse embryonic stem cells. These covariations form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariations and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariations. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex formation. Our results lend support to the concept of post-transcriptional RNA operons, but we further present evidence that nuclear proximity of genes may provide substantial functional regulation in mammalian single cells.
Collections
Subject
Animals
Cell Line
Cell Nucleus
Gene Expression Profiling
Gene Expression Regulation
Gene Knockout Techniques
Gene Regulatory Networks
Genetic Variation
Mice
MicroRNAs
Mouse Embryonic Stem Cells
Protein Interaction Maps
RNA-Seq
Ribonuclease III
Single-Cell Analysis
Transcription Factors
Transcriptome
Research team
Directorate for CEC
Language
eng
Date accepted
2020-09-15
License start date
2020-10-28
Citation
Nature Communications, 2020, 11 (1), pp. 5445 -
Publisher
NATURE RESEARCH