Nuclear Retention of mRNA in Mammalian Tissues

•Genome-wide catalog of nuclear and cytoplasmic mRNA in mouse tissues•Spliced, polyadenylated mRNA is retained in the nucleus for many protein-coding genes•Retained genes include ChREBP and liver Nlrp6, co-localized with nuclear speckles•Nuclear retention of mRNA reduces cytoplasmic gene expression noise

SummarymRNA is thought to predominantly reside in the cytoplasm, where it is translated and eventually degraded. Although nuclear retention of mRNA has a regulatory potential, it is considered extremely rare in mammals. Here, to explore the extent of mRNA retention in metabolic tissues, we combine deep sequencing of nuclear and cytoplasmic RNA fractions with single-molecule transcript imaging in mouse beta cells, liver, and gut. We identify a wide range of protein-coding genes for which the levels of spliced polyadenylated mRNA are higher in the nucleus than in the cytoplasm. These include genes such as the transcription factor ChREBP, Nlrp6, Glucokinase, and Glucagon receptor. We demonstrate that nuclear retention of mRNA can efficiently buffer cytoplasmic transcript levels from noise that emanates from transcriptional bursts. Our study challenges the view that transcripts predominantly reside in the cytoplasm and reveals a role of the nucleus in dampening gene expression noise.

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