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RNA. 2018 Jan;24(1):98-113. doi: 10.1261/rna.063172.117. Epub 2017 Oct 27.

CeFra-seq reveals broad asymmetric mRNA and noncoding RNA distribution profiles in Drosophila and human cells.

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Institut de Recherches Clinique de Montréal (IRCM), Montréal H2W 1R7, Canada.
Département de Biochimie, Université de Montréal, Montréal H3C 3J7, Canada.
McGill School of Computer Science, McGill University, Montréal H3A 0E9, Canada.
Institut de Recherches Clinique de Montréal (IRCM), Montréal H2W 1R7, Canada
Division of Experimental Medicine, McGill University, Montréal H4A 3J1, Canada.


Cells are highly asymmetrical, a feature that relies on the sorting of molecular constituents, including proteins, lipids, and nucleic acids, to distinct subcellular locales. The localization of RNA molecules is an important layer of gene regulation required to modulate localized cellular activities, although its global prevalence remains unclear. We combine biochemical cell fractionation with RNA-sequencing (CeFra-seq) analysis to assess the prevalence and conservation of RNA asymmetric distribution on a transcriptome-wide scale in Drosophila and human cells. This approach reveals that the majority (∼80%) of cellular RNA species are asymmetrically distributed, whether considering coding or noncoding transcript populations, in patterns that are broadly conserved evolutionarily. Notably, a large number of Drosophila and human long noncoding RNAs and circular RNAs display enriched levels within specific cytoplasmic compartments, suggesting that these RNAs fulfill extra-nuclear functions. Moreover, fraction-specific mRNA populations exhibit distinctive sequence characteristics. Comparative analysis of mRNA fractionation profiles with that of their encoded proteins reveals a general lack of correlation in subcellular distribution, marked by strong cases of asymmetry. However, coincident distribution profiles are observed for mRNA/protein pairs related to a variety of functional protein modules, suggesting complex regulatory inputs of RNA localization to cellular organization.


RNA localization; RNA-sequencing; cellular organization; messenger RNA; noncoding RNA; subcellular fractionation

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