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RNA

Follow the SINE for nuclear localization

Nature Reviews Genetics volume 19, pages 188–189 (2018)Cite this article

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Under the assumption that nuclear RNAs can carry sequences that direct them to the nucleus, Lubelsky and Ulitsky designed a 5,511 sequence library of 'tiles' of 109 nucleotides (nt) in length cloned into the 5′ and 3′ untranslated regions (UTRs) of a GFP mRNA. The tiles comprised fragments that span the exons of 37 lncRNAs, 13 3′ UTRs of nuclear-enriched mRNAs and four homologues of the lncRNA MALAT1, which is found in abundance in the nucleus. This library was transfected into cells of the breast cancer cell line MCF7, and the abundance of GFP mRNA and identity of each specific tile were determined by sequencing of nuclear, cytoplasmic and whole-cell extracts.

In this initial experiment, 19 regions (from 14 genes) were found to contain sequences that led to at least 30% greater nuclear retention than control GFP mRNA, most notably sequences derived from the lncRNAs JPX, PVT1 and NR2F1-AS1. The authors determined a consensus sequence for this nuclear localization signal: three stretches of six pyrimidines within a 42 nt sequence context, containing the sequence RCCTCCC (where R stands for A or G) at least twice. These sequences were found to overlap in antisense orientation with Alu repeat sequences — the most frequent short interspersed elements (SINEs) in the human genome. The authors termed them SIRLOIN, short for SINE-derived nuclear RNA localization. SIRLOIN elements were also enriched in nuclear fractions in public RNA sequencing data sets of ENCODE cell lines. Furthermore, they were present not just in lncRNAs but also in internal exons of nuclear-enriched mRNAs, suggesting that SIRLOINs may represent a universal mechanism of nuclear localization.

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References

  1. Lubelsky, Y. & Ulitsky, I. et al. Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells. Nature https://doi.org/10.1038/nature25757 (2018)

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  1. Associate Editor, Nature Communications,

    Michelle Trenkmann

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  1. Michelle Trenkmann
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Trenkmann, M. Follow the SINE for nuclear localization. Nat Rev Genet 19, 188–189 (2018). https://doi.org/10.1038/nrg.2018.10

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